Biology of the Supporting Tissues There's no art to find the mind's construction in the face. Shakespeare, Macleth INTRODUCTION . Throughout postnatal development and adult life, bone constitutes the princi- pal supporting tissue for the head and face. Cartilage, in contrast, is most prominent during prenatal development. During this time, it affords temporary support for the brain, midface, and mandible. Although the majority of cartilage has either atrophied or been converted to bone by the time of birth, sites of cartilage remain in the postnatal skull which contribute significantly to postnatal growth. Cartilage The above description of cephalofacial cartilage is applicable to the rest of the body. Although the volume of cartilage is very small compared to bone, it functions in ways that the latter tissue cannot. Cartilage is able to withstand compressive forces, and thus Osscous tissue, although capable of supporting consider buffered from direct articulation; in instances of direct One is continually reminded in the sports pages how cs ge damage shortens ers of gifted athletes. Bone rubbing on bone is destructive and painful. Cartilage, on the other hand, is designed for articulation and intermittent load- ing. It is resilient, acting to absorb and dissipate shock. Cartilage possesses this property by virtue of a tough, hydrophilic matrix which swells with tissue s found on the surfaces of the bones of joints. ble loads, must be Ds res the c:6 A SYNOPSIS OF CRANIOFACIAL GROWTII fluids—much like a sponge fills with water. When loaded, the fluid is ex- pressed; when unloaded, the fluid is drawn buck in. This egress and ingress of fluid not only cushions the forces of articulation, it also nourishes the cartilage cells. The continuous perfusion of the cartilage supplants the need for a vascular system, The advantage of a seemingly primitive system for the transport of nutrients and waste products is that cartilage can never suller from an inter- rupted blood supply as a result of compressive occlusion In addition to its resiliency, cartilage possesses the ability to expand from within, This property, called interstitial growth, means that cell division, ma- trix deposition, or a combination of both, can take place within the tissue. Cartilage is not limited to surface apposition like bone because it is not calcified and because its matrix ean expand to accommodate new cells and new ex- tracellular secretions, Interstitial expansion is critical to human growth. Virtu- ally all longitudinal growth of shafted bones results froin strategically located slices of cartilage which expand by this mechanism. These centers of growth, called growth plates, can form new tissue under the rigors of body weight, something impossible for bone. Cartilage is also present at critical sites in the cephalofacial complex, but in some locations it may be less concerned with load- bearing growth as with other functions. This subject will be discussed more fully in the sections titled Cells of Cartilage and Methods of Bone Formation, below. Bone Osseous tissue, as it has evolved into the many bones of the skeletal system, provides incredibly strong support with a minimal weighUstrength ratio. This is accomplished by a combination of molecular and morphologic configurations which only in modern times have humans been able to duplicate in manufactur- ing and construction. For instance, the inclusion of collagen fibers in a calcified matrix long preceded the incorporation of steel rods in concrete; the structure of the cranial vault, with inner and outer dense cortices separated by cancellous bone, closely resembles modern high-technology panel construction where two layers of fiberglass are separated by a light foam material Yet, despite being a strong and rigid tissue, bone is highly malleable to certain cells, and as we shall see, considerable remodcling occurs during the growth process. It is this combi- nation of strength and moldability that makes bone so unique and so important to the student of craniofacial growth. COMPOSITION OF SUPPORTING TISSUES Matrix Histologically, bone and cartilage can readily be differentiated. Not only is bone calcified, but its internal architecture and variety of cells is quite distinct. The dissimilarities between these tissues are rooted in subtle differences at the molecular level. While the matrices of both tissues are composed of collagenBIOLOGY OF THE SUPPORTING TISSUES 7 and protein-carbohydrate complexes, variations in these molecules are funda- mental to the form and function of the tissue. Thus, bone is not simply mineral- impregnated cartilage, although such a stage is fundamental to the transition from one to the other. Rather, the conversion from cartilage to bone requires a complete turmover in matrix, as well as changes in cell types, mineral content, and orgar To better understand the nature of cartilage and bone and the transition process, an overview of the molecular profile and their functional importance will be presented tion Collagen. The major organic constituent of cartilage and bone is collagen. It is essentially protein, save for a few important carbohydrate side-groups. The term collagen includes any molecule that contains a typical helical conformation and that also participates in the formation of extracellular supramolecular aggre gates whose primary function is support. There are at least 11 different types of collagen, of which types I and II, found in bone and cartilage respectively, are the most studied. In most cases it appears that collagen exists as fibers. The orientation of these fibers is peculiar to a specific tissuc, appropriately provid- ing support within the context of its form and function. In the electron microscope, the fibers of collagen type I display a charac- teristic pattern of cross-striations, or bands (Fig. 1-1). The most prominent cross-striations are about 680 A apart and have been ascribed to the specific parallel alignment of the basic molecular units of collagen. These units, with the dimension of a rod 15 A in diameter and 3000 A long, are aligned in a quarter stagger. Becuiise these units are staggered in relation to their neigh- bors, there are zones of overlap at both ends. These overlap areas afford opportunities for cross-linking, thereby tying all the rods together and forging fibrils of great strength. The periodicity of the bands is thought to be duc to five charged regions on the collagen molecules, which, when registered with others in a precise array, stain in the characteristic 680 A pattern. Figure 1-1. Diagrammatic repre- weccrorisni. sentation of collagen structure. (A) A ino The cross-striations of the micro- : ita fibril with the regular repeat of 680 A, (B) A two-dimensional view of the alignment of collagen units forming the microtibril. (C) The es- sential dimensions of the rodiike unit collagen. (D) The formation of collagen by the aggregation of three polypeptides called alpha chains. (Adapted from M.E. Grant and D.J. Prockop: The biosynthe- sis of collagen. New Eng. J Med 286:194, 1972.)YY Y a eens 8 ASYNOPSIS OF CRANIOFACIAL GROWTH nn unit consists of three polypeptide chains of approxi- individually and collectively, are h of these polypeptide subunits is The basic collage! mately 1000 amino acids each. These chains, coiled in unique, rigid, helical structures. Eacl called an alpha chain. Whenever possible, collagens are identified according to the amino acid sequence of the individual chains and their pattern of aggrega- tion. A seemingly complex nomenclature is necessary since there are at least 19 genetically different alpha chains which compose the 11 known collagens. For instance, the collagen molecule may consist of three identical alpha chains and thus be designated as (a1],; if the collagen unit consists of two identical alpha chains and another that differs in amino acid sequence, it is abbreviated as {al],a2. To show that the composition of the alpha one chain of (a1); differs from the alpha one chain of [a1],42, roman numerals are added to the symbol, for example, [a1(1)], and [al(11)},02. Type I collagen is prevalent in most connective tissues including bone and dentin. It is a heterotrimeric molecule composed of two identical a1(1) and an 22(1) chains. Virtually every third amino acid of each of these chains is glycine. Because glycine is the smallest of the amino acids, it can assume the center position of a helix. In addition to the individual coiling, the three alpha chains coil around each other in a superhelix. The amino acid sequence thus sets the stage for the rodlike conformation of collagen and its propensity to align in microfibrils. Each of the alpha chains possesses two nonhelical amino acid sequences called telopeptides. These segments, one at each end, are globular and consider- ably shorter than the helical portions. The high lysine content of the telo- peptides is thought to be crucial to cross-linking; they may stabilize the parallel arrangement of the collagen units. In the alignment of collagen molecules to form the microfibrils, there is a gap or “hole” of about 410 A occurring between the end of one unit and the beginning of the next. These hole zones have been implicated as sites of initial calcium hydroxapatite deposition. Following calcification of bone, approxi- mately 50 percent of all the mineral is found in these holes. The fibrils seen in bone are fairly uniform in size and highly oriented. In et ie cles for example, they are organized in alternating sheets, becomes aca ers a pywood. When impregnated with mineral, the tissue Wiallos ne oe renee os sompresevs and tensile strength. ed of with the formula [a1(1)},, While eh othe ee a homology with the chains of type I collage: Dis chals) 5951 considerable land aie ype I collagen, they are more highly hydroxytated these oe ate ), rendering them more bulky and hydrophilic. Evi Hse molecular differences are responsible for the electron micros of cartilage fibrils: variability of size, | riage rindomrorlefitatiot, Th y of size, lack of cross-stviations, branching, “sponge” to ae i re apparent function of cartilage colla the fibers abtorhe compress netted Proteoglycan m s compressive loads. and en is to hold the és interspersed between Althou, ¢ hole zones exist in cartila y apparently gh § exist in cartilage collagen, they are apyBIOLOGY OF THE SUPPORTING TISSUES 9 obscured by other proteins which prevent calcification. In certain pathologic conditions and during the transformation to bone, cartilage is calcified; its role othenwise is to remain unealcified and resilient. Proteoglycans. The other major organic constituent of cartilage and bone con- sists of protein-carbohydrate complexes formed by the covalent linkage of glucosaminoglycans (GAG) to protein cores. The GAGs (formerly known as acid mucopolysaccharides) are highly charged polyanions composed of repeat- ing disaccharide units bearing either a sulfate or a carboxyl group, or both Eight’ of these complex molecules have been studied: hyaluronate, chon- droitin, 4-sulfate, chondroitin 6-sulfate, skeletal keratin sulfate, dermatan sul- fate, heparan sulfate, corneal keratan sulfate, and heparin. The first four are found in cartilage. These disaccharide chains are subunits of large and complex aggregates called proteoglycans. Approximately 100 chondroitin sulfate and 50 keratin sulfate molecules are organized along a protein core which has a molecular weight (MW) of 250,000 to 350,000 (Fig. 1-2). The molecule formed by the GAGs and protein core resembles a bristle brush designed for cleaning bottles. The total MW of a proteoglycan monomer (a core protein and the chains cova- lently bound to it) is 1.5 to 2.5 million. These core proteins in turn are attached toa large GAG, called hyaluronic acid, by smaller proteins, called link proteins. Approximately 100 core proteins are bound to each hyaluronic acid chain. The total weight of all these proteoglycans aggregated on hyaluronic acid can amount to tens of millions. The dimensions of this complex in vitro are equiva- lent in size to the mitochondria of a cell. In articular cartilage, at least, it is packed more tightly, presumably at a size optimal for maximum resiliency. Protein Core Chondroitin ‘Sulfate Chains Keratan Sulfate, Chains +D-Link Protein Hyaluronic , Acid Figure 1-2. Diagrammatic representation of the structure of cartilage proteo- glycans. (From Buckwalter JA: Proteoglycan structure in calcifying cartilage. Clin Orthop 172:207, 1983, with permission.)10 ASYNOPSIS OF CRANIOFACIAL GROWTH! The net result of this claborate complex is an ability to structure water Proteoglycans are extremely large but highly ordered arrays of electroneg- ativity. Because water is a small clectric dipole, electrostatic forces such as those possessed by proteoglycans can govern the interactions of water mole- cules with themselves and with other molecules. As a result, water can be organized in shells around a focus of electric charge and, in a sense, become “structured.” Utilizing the thousands of negatively charged sulfate and carboxyl moieties of GAGs, the proteoglycans in cartilage can structure large volumes of water—many times their own weight. This structuring of water has important implications in growth. First, of course, when pressure is applied, water is forced away from the charged do- mains of the GAGs. When these negative charges come into close proximity, repulsive forces prevent further compression. When the pressure is released, water is reattracted by the same charges. Accordingly, cartilage is util ized in centers where growth must occur under load and cells must be nourished by perfusion. Second, the secretion of proteoglycans during embryologic development “captures” space for tissue growth. This means that when these aggregates are transported extracellularly, they swell massively as they structure water. A consequence of this high water/matrix ratio is a porous environment for the infiltration of other cell types. The immigrant cells divide and populate the interstices—and in time create a new tissue. Thus, proteoglycans permit a few cells to wedge out a disproportionate amount of space within a cell mass for the development of new tissues. Although the investigation of bone proteoglycans has been hampered by the difficulties attendant to a calcified tissue, it is clear from preliminary find- ings that the size of bone proteoglycans is smaller and more variable than those in cartilage. Several reasons can be advanced to explain these differences. First, the formation of bone does not demand the capture of large amounts of space When bone is derived from a cartilage precursor (endochondral bone forma- tion), space has already been gained by the cartilage; when new bone is formed directly (intramembranous bone formation), the process is slower and the need for space is less. During remodeling of bone where volumes do not change dramatically, the hydrodynamic properties of proteoglycans are unnecessary. Second, when bone calcifies, it no longer has need for resiliency, and the content of bone proteoglycans can be reduced. Intriguingly, the lower levels of proteoglycans aid the process of calcification, since the electronegativity of the GAGs prevents calcium hydroxyapatite formation. Thus, water structuring and inhibition of calcification—properties that are vital to cartilage function— become coincidentally unnecessary for bone. In the transformation of. cartilage to bone, the reduction in proteoglycans not only heralds a modification of function, but it also helps ensure the change by diminishing inhibitory influences—a beautifully integrated system, indeed! Presumably, the small proteoglycans that bone does possess are sufficient to aid in the orientation of collagen fibrils.MOLOGY OF THE SUPPORTING TISSUES, uW sous once hone is fully formed Finally, since proteoglycans become extra and mature, itis likely that enzymes degrade them In recent vears a number of noncollagenous proteins have | in the matrix of cartilage and bone that clearly do not have a structural role. Some of them, such as tivity and bone morphogene! protein, are purported to have inductive propertics. Thus, the matrices of cartilage or bone may possess the molecular seeds for their own replacement should they be interrupted by cell resorption or trauma. There is evidence that bone morphogenetic protein can be used to promote wound repair in bones; someday it, or other factors to be discovered, may contribute to the manage: ment of growth on a localized basis. en discovered rtilage stimulating a The Cells of Bone Bone is the fundamental supporting tissue of the body. The composition of the matrix and the percentage of calcium hydroxyapatite impregnation relative to the organic constituents is consistent throughout the bones of an individual, What differs within and between bones occurs at morphologic and histologic levels. Most bones, whether in limbs or the head, possess at least one surface of dense bone called compact or cortical bone. Interior to the compact layer is usually found cancellous or spongy bone (Fig. 1-3). The porous texture of the cancellous portion permits the interspersion of hematopoietic stem cells and connective tissues among the trabeculae of bone: CANCELLOUS. BONE PERIOSTEUM ENDOSTEUM Figure 1-3. The two principal morphologic divisions of bone—compact and can- cellous.12 ASYNOPSIS OF CRANIOFACIAL GROWTH Important inhabitants of the bone marrow are the surface osteoblasts, which form a loose synctium over all of the internal bone tissue. This network of cells, called the endosteum, although not anatomically tight, works in concert to regulate the exchange of solutes between body and bone fluids. The outer covering of bone, the periosteum, is clearly a structural entity, fully capable of being peeled away intact from the underlying calcified tissue. The periosteum is a sheath composed of an outer laycr of fibrous connective tissue and an inner layer of surface osteoblasts next to the bone. The compact bone sandwiched between the periosteum and endosteum is nourished by a complex vascular system involving blood vessels and minute avascular canals within the bone. Further description of this complex system and its role in bone remodeling will be found in the discussion of the bone cells below. There are three classes of bone cells: the osteoblasts, the osteocytes, and the osteoclasts. Considerable information about these cells has been gained in recent years. The functions ascribed to each are generally accepted; the lineage of each type has been firmly established. The osteoblast. This cell is responsible for the synthesis of the extracellular matrix of bone (the collagen and proteoglycans) and the initiation of calcifica- tion. The osteoblasts are generally incapable of cell division and must arise by modulation from precursor mesenchymal cells. An active osteoblast is columnar in shape and is characterized by the following organelles: a single nucleus, an elaborate endoplasmic reticulum, a well-developed Golgi apparatus, and many mitochondria. These are the ear- marks of a cell engaged in synthesis The osteoblast is a surface cell found in the deep layer of the perios- teum, around the trabeculae, or lining the canals of the haversian system. As they deposit the matrix, the osteoblasts retreat, maintaining for a time their positions on the surface. Eventually the cells cease their unilateral secre- tion and envelop themselves in their own juices. Once osteoblasts become buried within the bone, they are called osteocytes. During the secretive stage, the cell membranes of the osteoblasts extrude numerous tentacle-like Pro- cesses in all directions. These processes establish and maintain cell contact even after bone is calcified. Thus, fluid and solutes can move through the canaliculi housing the processes, nourishing the osteocytes, and removing the waste products. The osteoblast manufactures the collagen on the ribosomes locat the endoplasmic reticulum. Linear peptides (called propeptides) of alm« amino acids are initially synthesized The final extruded length i less since one-third of the amino acids are removed during intrace ing, By virtue of different amino acid sequences, two pept 2:1 stoichiometric relationship. Two pro-L and one pro triple helical structure called preprocollagen, and thes within the cisternae of the reticulum. From her ur process s are produced in a peptides unite in a les accumulate these molecules are trans-MOLOGY OF THE SUPPORTING TISSUES, 13 ported to the Golgi apparatus. At some point the N-terminal and C-terminal propetides are cleaved and procollagen is expelled extracellularly. After expulsion, remaining nonhelical terminal portions of the procollagen are cleaved by a peptidase. These nonhelical ends, called tclopeptides, are thought to aid in the extrusion or alignment of procollagen. The smaller mole- cule remaining after the cleavage has a MW of approximately 300,000 and is called the basie collagen unit Radivactively labeled precursors have been used to verify that the oste- oblasts are also responsible for the synthesis of the proteoglycans. In addition to the synthesis of matrix, osteoblasts initiate calcification. They accomplish this process by releasing membrane vesicles into the matrix that have the capacity to nucleate calcium hydroxapatite crystals. The osteocyte. Osteocytes are easily identified by two characteristic features ()) they reside within chambers called lacunae, and (2) they exhibit numerous cytoplasmic projections radiating about in fine channels called canaliculi. The extremely large area of the cell membrane-bone tissue interface obtained by this system is crucial to the control ‘of calcium homeostasis, the principal func- tion of osteocytes. Most osteocytes reside indefinitely in mature bone unless they are freed during remodeling resorption. Some osteocytes complete an identifiable life cycle that can span many years, beginning with envelopment and ending with cell death. Soon after the osteocyte is entrapped within its lacunae, the organ- elles still resemble and function like those in the osteoblast. Accordingly, this has been called the formative phase. As the cell matures, the Golgi complex and its associated vesicles become more prominent, suggesting a rise in lysosomes to aid in the resorptive phenomenon. In a process unique to osteocytes, called osteolysis, mineral is withdrawn from and returned to the matrix surrounding the lacuae and canaliculi, providing calcium for the minute-to-minute control of mineral homeostasis. During the process, the matrix is demineralized and often viewed by transmission electron microscopy. Should the stimulus for osteolysis be prolonged, several lacunae can become confluent, with the result that their osteocytes are released. The last stage of the osteocyte’s life is degenerative, characteri: vacuolization of cell organelles, cell death, and disintegration. The osteoclast. The cell most responsible for the resorptive aspe bone remodeling is the osteoclast. It is classically associated with erosion pits called Howship's lacunae resulting from a resorptive process called osteockasis. Act ally, the osteoclast is capable of removing bone from any surface with or without pit formation. The osteoclast is the most fascinating of the bone cells, poss: an exceptional size and unusual presentation of organe history. sing not only Hes, but an enigmatic life This cell can have multip nuclei ing in number from 2 to over 100.14 A SYNOPSIS OF CRANIOFACIAL GROWTIE The size of the cell increases proportionally, and as a result, the giant osteoclast can be the largest cell in the body. Besides the abundance of nuclei, the characterized by a plethora of mitochondria and a unique aggrega- tion of centrioles called the centrosphere One of the most distinguishing features of an osteoclast is the specialized cell membrane found at the site of bone resorption called the ruffled border. It is a complex zone of folds and cytoplasmic projections contiguous to the resorbing matrix. The extensions are only fractions of a micron wide but may be several microns long. The spaces between these folds are tortuous and often show matrix debris between them when viewed by transmission electron mi- croscopy. The folds terminate as vesicles or vacuoles that have been reported to contain apatite crystal. Encireling the rufled border is a clear zone where the cell membrane is smooth and adapted to the contour of bone. It has been suggested that this circular zone attaches to bone and delimits the area of resorption; it might be responsible for the localized resorption seen in Howship’s lacunae. While the clear zone at the periphery of the rufiled border does not attain a perfect scal against bone, it probably does establish the basis for a microenvironment. The process of bone resorption at the ruffled border probably entails physical as well as enzymatic activities—the clear zone concentrates and focuses these efforts. The origin of the osteoclast has become clearer in recent years. While it was long accepted that osteoclasts arise from the fusion of smaller cells, the origin of these cells was unresolved. Some investigators have maintained that the precursor cells of the osteoclast have the same lineage as that of osteoblasts, that is, mesenchymal cells. Others have proposed that osteoclasts derive from a fusion of wandering mononuclear phagocytes. Recent reports from a number of laboratories strongly support the latter theory (see Bonucci). The stimuli for osteoclasis is multifactorial. Certainly bone necrosis trig- gers osteoclastic resorption, as does excess parathyroid hormone. Relative to bone remodeling, the stimulus is possibly related to electrical activity engen- dered in the bone by the bending associated with function. It is known that bone deformation leads to the development of electric potentials, presumably a piezoelectric effect. How such signals are translated into the many activities of ostcoclasis has not been determined. osteoclas: The Cells of Cartilage ‘The cartilage responsible for active growth is called hyaline Ussue is derived from mesenchyme by a condensation of me: which promotes their differentiation into matrix synth: chondroblasts. As the chondroblasts divide and secrete expands and compresses the surrounding mesenchy fibrous envelope develops called the perichondriu outer fibrous layer and a cellular inner layer of pr have the potential to differentiate into chondrobl. trix, the tissue As a result, a cath has a tough ts. These cells asts which can synthematrix, The deposition by perichondral chondroblasts is unidir results in sur apposition. The chondroblasts within the mesenchymal con- ensation have no polarity, and consequently they surround themselves with their own seerctions. At this point they arc called chondrocytes. T he change in name is based more on histologic than functional criteria, however, for these chondrocytes can continue to divide and synthesize new matrix, Cartilage there- fore retains the pote to increase in size by two mechanisins, interstitial expansion and peripheral apposition, Chondrocytes of mature hyaline cartilage are often seen in small clusters, suggesting that some mitoses occur at a time when the matrix is more rigid and unable to accommodate the separation of the daughter cells (Fig. 1-4) Chondrocytes reside in lacunae, but without processes radiating out in ca- naliculi, When not crowded, chondrocytes tend to be ovoid cells with a round nucleus. Since they are secretory cells they possess rough endoplasmic reticu- Jum (RER) and a well-developed Golgi complex. They are also characterized by lipid droplets, glycogen granules, and intracellular microfibrils in adddition to the usual organelles: Although the cartilage-forming cells have been rather extensively studied, relatively little is known about chondroclasts, the cells that resorb cartilage. Like osteoclasts, they are multinucleated giant cells that originate from multiple fu- sions of smaller cells. Unlike their osseous counterparts, chondroclasts exhibit less prominent brush borders and less intimacy with resorptive lacunae. In fact, one chondroclast may span several lacunae, but with scattered points of contact. Functionally, the two kinds of clasts may be very similar, since crystals have been described within the vacuoles of chondroblasts involved in the resorption of calcified cartilage. While the lineage of osteoclasts is clearly from monocytic macrophages, nothing is known about the origin of the chondroclasts. It has been argued that the distinction between these giant resorptive cells bbsipin hs ema wa tee ores tiatingey risctate ‘matrix formation14 ASYNOPSIS OF CRANIOFACIAL GROWTH The size of the cell increases proportionally, and as a result, the giant osteoclast can be the largest cell in the body. Besides the abundance of nuclei, the osteoclast is characterized by a plethora of mitochondria and a unique aggrega- tion of centrioles called the centrosphere One of the most distinguishing features of an osteoclast is the specialized cell membrane found at the site of bone resorption called the ruffled border. It is a complex zone of folds and cytoplasmic projections contiguous to the resorbing matrix. The extensions are only fractions of a micron wide but may be several microns long. The spaces between these folds are tortuous and often show matrix debris between them when viewed by transmission clectron mi- croscopy. The folds terminate as vesicles or vacuoles that have been reported to contain apatite crystal. Encircling the rufHed border is a clear zone where the cell membrane is smooth and adapted to the contour of bone. It has been suggested that this circular zone attaches to bone and delimits the area of resorption, it might be responsible for the localized resorption seen in Howship’s lacunae. While the clear zone at the periphery of the ruffled border does not attain a perfect seal against bone, it probably does establish the basis for a microenvironment. The process of bone resorption at the ruffled border probably entails physical as well as enzymatic activities—the clear zone concentrates and focuses these efforts. The origin of the osteoclast has become clearer in recent years. While it was long accepted that osteoclasts arise from the fusion of smaller cells, the origin of these cells was unresolved. Some investigators have maintained that the precursor cells of the osteoclast have the same lineage as that of osteoblasts, that is, mesenchymal cells. Others have proposed that osteoclasts derive from a fusion of wandering mononuclear phagocytes. Recent reports from a number of laboratories strongly support the latter theory (see Bonucci). The stimuli for osteoclasis is multifactorial. Certainly bone necrosis trig- gers osteoclastic resorption, as does excess parathyroid hormone. Relative to bone remodeling, the stimulus is possibly related to electrical activity engen- dered in the bone by the bending associated with function It is known that bone deformation leads to the development of electric potentials, piezoelectric effect. How such signals are translated osteoclasis has not been determined. presumably a nto the many activities of The Cells of Cartilage ‘The cartilage responsible for active growth is called hyaline cartilage. This ussue is derived from mesenchyme by a condensation of mesenchymal cells, which promotes their differentiation into matrix synthesizing cells called chondroblasts. As the chondroblasts divide and secrete a matrix, the tissue expands and compresses the surrounding mesenchymal tissue. As a result, a fibrous envelope develops called the perichondrium. This sheath has a tough outer fibrous layer and a cellular inner layer of prechondroblasts. These cells have the potential to differentiate into chondroblasts which can synthesize newBIOLOGY OF THE SUPPORTING TISSUES, 15 matrix. The deposition by perichondral chondroblasts is unidirectional and results in surface apposition. The chondroblasts within the mesenchymal con- densation have no polarity, and consequently they surround themselves with their own secretions. At this point they are called chondrocytes. The change in name is based more on histologic than functional criteria, however, for these and synthesize new matrix. Cartilage there- in size by two mechanisins, interstitial chondrocytes can continue to divide fore retains the potential to incre: expansion and peripheral apposition. Chondroeytes of mature hyaline cartilage are often seen in small clusters, suggesting that some mitoses occur ata time when the matrix is more rigid and unable to accommodate the separation of the daughter cells (Fig. 1-4) Chondroeytes reside in la , but without processes radiating out in ca- naliculi. When not crowded, chondrocytes tend to be ovoid cells with a round nucleus. Since they are secretory cells they possess rough endoplasmic reticu- Jum (RER) and a well-developed Golgi complex. They are also characterized by lipid droplets, glycogen granules, and intracellular microfibrils in adddition to the usual organelles. Although the cartilage-forming cells have been rather extensively studied, relatively little is known about chondroclasts, the cells that resorb car tilage. Like osteoclasts, they are multinucleated giant cells that originate from multiple fu- sions of smaller cells. Unlike their osseous counterparts, chondroclasts exhibit less prominent brush borders and less intimacy with resorptive lacunae. In fact, one chondroclast may span several lacunae, but with scattered points of contact. Functionally, the two kinds of clasts may be very similar, since crystals have been described within the vacuoles of chondroblasts involved in the resorption of calcified cartilage. While the lineage of osteoclasts is clearly from monocytic macrophages, nothing is known about the origin of the chondroclasts. It has been argued that the distinction between these giant resorptive cells ma CELL pivision MATRIX FORMATION Interstitial expansion in cartitag matrix formation. sulting from cell division and new16 ASYNOPSIS OF CRANIOFACIAL GROWTT is arbitrary. Perhaps the generic word mineraloclast might be preferable to osteoclast, chondroclast, dentinoclast, and cementoclast. METHODS OF BONE FORMATION The deposition and calcification of bone tissue can occur in one of two ways, that is, directly (intramembranous) or indirectly (endochondral). Even though the terms intramembranous and endochondral are more historical than descriptive, their use is so ingrained in the literature that they will be used interchangeably with more meaningful terminology. In intramembranous formation (or direct osteogenesis), osteoblasts secrete matrix and initiate calcification. The indirect method (cartilage replacement) is more circuitous and involves the use of a cartilage precursor as a scaffold.on which to deposit bone. In this process, carti- lage is first formed by chondroblasts, undergoes mineralization, and then is invaded by bone resorbing cells, which reduce the matrix toa framework. Next, the osteoblasts, which have differentiated from the invading vasculature tissue, deposit bone matrix around the cartilage model. The second time it occurs in bone, anew architecture of tissue is established. Eventually, the remnants of the cartilage matrix are completely lost in the process of growth and remodeling. While the cartilage replacement mechanism is less efficient than direct osteogenesis, it has been selected by nature for two important reasons. The first results from the limits on new bone formation imposed by the nature of the bone itself. Because bone is calcified, there is no possibility of internal expan- sion due to cellular proliferation or matrix deposition. This Property, interstitial expansion, is characteristic of soft tissues, including cartilage (see Fig. 1-4). Chondrocytes can thus undergo cell division and secrete matrix, rapidly form- ing new tissue mass, which is subsequently converted to bone. Of equal impor- tance is the directionality of cartilage growth. In some cartilage replacement sites such as the growth plates, cells and mitotic activity are highly oriented, and growth is essentially unidirectional (Fig. 1-5). The nature of direct osteo- genesis, on the other hand, does not lend itself to genetic predetermination. A second factor responsible for the indirect method of bone formation is the inability of bone cells to form new tissue while under pressure. This last statement does not imply that bone cannot withstand a load, which of course it can (we are not shapeless piles of protoplasm), nor does it mean that bone apposition cannot occur in a load-bearing situation, that is, the thickness of the cortex of a long bone increases with age through the process of apposition. What it does say is that direct pressure on the periosteum, as might occur if the articular surfaces of two bones at a joint were composed of this tissue, as inhibit new apposition and lead eventually to degeneration, resorption or . th As has been discussed above, the matrix of eartilage permits nouris monty erfusion and interstitial expansion. Thus, cartilage of the joint can withstan the rigors of articulation, and hyaline cartilage of the yrowth plates can grow under load.BIOLOGY OF THE SUPPORTING TISSUES 17 ENDOSTEUM PERIOSTEUM SYNOVIAL FLUID LOOSE ARRANGEMENT : ARTICULAR OF CARTILAGE CELLS COLUMNAR ARRANGEMEN’ OF CARTILAGE CELLS Figure 1-5. Cross section of a limb of cartilage. joint of a child illustrating the remaining areas The ability of cartilage to grow against a load is aptly demonstrated by the growth plates of the long bones of the legs, which continue to lengthen despite the weight imposed on them by the torso and head. Intramembranous Bone Formation Intramembranous bone formation occurs on the outer surface of the perio- steum, the endosteum, on the surfaces of trabeculae of cancellous bone, and in the case of a few bones in the skull, at the edges in specialized structure: sutures. 's called Periosteum and endosteum of the cortex. The inner zone of the periosteum is populated by osteoblasts and osteoblast precursor cells. For some period of time, the osteoblasts secrete matrix, and the periosteum drifts away as the bone thickens (Fig. 1-6). At some point, these osteoblasts enclose themselves in their own secretions and become osteocytes. Other pre into osteoblasts to replace tl cursor cells differentiate em and the process continues. When resorption of bone is required during remodeling, periosteal osteoclasts presumably develop from blood-borne monocytes. As one might expect from the overall tendency of bone to enlarge during growth, the majority of periosteal activity is tional. Select sites of resorption are necessary to maint however. apposi- ‘ain bone conformation,18 A SYNOPSIS OF CRANIOFACIAL GROWTH RESORPTIVE PHASE OF OSTEON, HAVERSIAN SYSTEM Figure 1-6. The haversian system of mature, compact bone. The cortex formed in the prenatal and carly postnatal periods is called primary vascular bone. The name is derived from the highly vascular nature of the tissue and the uniformity of its appearance in contrast to mature bone. During cortical apposition, blood vessels that lie along the periosteum are entrapped in bony canals which run parallel to the surface of the bone. The circumference of these canals is at first larger than necessary for the size of the enclosed vessels, but they soon narrow by centripetal apposition of surface osteoblasts. In a cross section the circumferential lamellar pattern of bone deposition within these canals contrasts sharply with the rest of the cortex. These long cylinders of bone with a vascular core are called primary osteons (see Fig. 1-6). In adult bone they are called secondary osteons because they are products of remodeling and not original osteogenesis. Osteons serve at least two functions: they house blood vessels that nourish blood cells, and they permit internal modification of the cortex as an adaption to new stresses. The endosteum does not exhibit the capsular connective tissue of the periosteum, but rather consists of a looser arrangement of osteoblasts and vari- ous pluripotential cells capable of differentiating into hematogenous, osseous, or connective tissue cell lines. The endosteum is primarily resorptive, since the normal pattern for long bones, for example, is to become thicker, thereby increasing the size of the marrow space. Asa rule, endosteal resorption does not parallel periosteal apposition; consequently the cortices of bones become thicker with time.BIOLOGY OF THE SUPPORTING TISSUES, 19) Cancellous bone. Cancellous bone is formed partly by continued apposition and resorption of the trabeculae in the marrow spaces. It is also formed by endosteal remodeling of the inner surfaces of the cortices as the marrow vol- umes increase during bone growth, Sutures. A suture is a type of joint in which the two apposed bones are so closely united by fibrous tissue that no movement can occur. Despite the rigidity of the junction, sutures are active sites for growth. Between the edges of bone are found connective tissue and a variety of cell types, including osteoblasts and osteoclasts. The older histologic description of the suture by Weinman and Sicher included three zones of cells, two associated with the edges of the bone, and one in the middle which is proliferative. This scheme dictates that proliferation in the middle zone contributes to both bones equally. A> corollary of this theory is that the bones are wedged apart by expansive growth in this zone. ‘These views of the suture, narrowly founded on histologic interpretations, have not held up to diverse scrutiny. The cur- rent concept of the suture depi it as a five-layered structure (ig. 1-7). The cambial cells are precursor cells that replace the osteoblasts as bone deposition occurs. The purported existence of the capsular layers isolating a middle zone of neutral cells means that the synthetic process of two bones are isolated from one another. Bone A has its own battery of cells responsible for sutura] deposition, and activity there is not necessarily reflected in similar cells of bone B. The division of labor within the suture is probably not as clear-cut as this description would indicate, but without question each bone can act inde- pendently of the other. In fact, bone on one side of the suture can undergo resorption while the apposing bone is in a state of apposition. The indepen- dence of the sutural surfaces allows for differential growth, whereby one bone of the skull might grow at a greater rate than its neighbor in response to uneven brain growth below. It is teviipting to categorize a suture as a specialized area of the periosteum In many cases this could legitimately be done. However, there are sutures that behave very unlike a periosteum. In the intermaxillary suture of the rat, as an extreme example, cartilage replacement rather than direct osteogenesis ac- counts for much of the growth. In the newborn rat the palatal processes of the Figure 1-7. Diagram of a suture as a five-layered structure. (After Pritchard JJ, Scott JH, Girgis FG: Structure and development of cranial and facial sutures. J Anat 90:73, 1956.)20 © ASYNOPSIS OF CRANIOFACIAL GROWTH maxilla meet at the midline, separated by a layer of closely packed undifferenti- ated cells. In a few days cartilage begins to form lateral to the suture; further from the midline this cartilage is converted to bone. Within 20 days the two cartilages unite across the suture, forming a synchondrotie junction. This suture continues to contribute to both shelves of the palate by interstitial expansior Eventually the cartilage in the midline is croded and a fibrous suture takes its place. There have been no reports of human sutures that complete synchon- drotic unions. The intermaxillary suture of the human, however, exhibits areas which resemble the presynchondriotic stage of the rat. The human sutures always displayed bilateral perichondral zones, divided by a narrow, intervening layer of vascular connective tissue. With age, the cartilage component disap- pears and the edges of bone become lamellar and smooth in appearance. Thus, in many cases cartilage contributes to sutural growth. Whether cartilage is genetically programmed to play a role, or whether it is produced by factors such as pressure, is unknown. Cartilage Replacement The growth plate—the classic model of endochondral bone formation. There are three cartilage replacement mechanisms in the Postnatal head, two of which are small remnants of the extensive cartilage chondrocranium of fetal development. Each of these mechanisms contributes in a special way to craniofacial growth. Because of their anatomic locations, which have compli- cated accessibility, and their relatively small tissue masses, which have hari *” pered biochemical analyses, more of our knowledge about cartilage replace- ment as a mechanism for bone formation has been derived from studies on the growth plate. This center for growth has thus become a standard to which other replacement mechanisms are compared. A discussion of the cartilage replacement sites of the head is facilitated by prior discussion of the growth plate. In addition, the reader's comprehension of later sections dealing with the endocrinology of craniofacial growth will be dependent on an understand- ing of its biology. Each growth plate is developed after extensive conversion of a cartilage limb bud into a bone (Fig. 1-8). The future bone begins embryonically as a cartilage anlage, or precursor. The cartilage cells differentiate alter being re- stricted by an enclosing perichondrium as described below. The cartilage cells are haphazardly arranged in this anlage, manifesting no specific orientation or direction of growth. Obviously, the amount of lincar growth that the limb undergo is limited by the randomness of cell activity. Durkin and colleagues have given the name “embryonic” to this type of cartilage, meaning that its role is to establish a territory and serve as a precursor for bone. Cartilage can also become specialized, that is, develop into a tissue with highly oriented cells, directed growth, and synchronous cell division and matrix deposition. As will be shown, these are the characteristics of the growth plate , The perichondrium around the middle of the anlage thickens eve a forming a perichondral ring, ‘This new constriction presumably diminishesBIOLOGY OF THE Si PPORTING TISSUES 21 Figure 1-8. The steps in the conversion of a cartilage anlage to a mature long bone. A. The cartilage anlage. B. After invasion by the blood supply (periosteal bud) at the middie of the anlage (diaphysis), the calcifying cartilage is progres sively converted into bone until only the ends remain cartilaginous (the epiph- yses). C. Sometime later, the epiphyses are invaded by separate blood supplies and the ends become bone tissue except for the growth plates and articular surfaces. D, upper. When longitudinal growth ceases sometime after puberty, the growth plates are replaced by bone and the diaphysis and epiphyses become continuous.(D, lower). (Adapted from Rubin P: Dynamic Classification of Bone Dyspiasias. Chicago, Year Book Medical, 1964.) perfusion, triggering a series of events that elicits mincralization of the cartilage in the middle of the shaft. Recently a low ilar-weight factor has been isolated from cartilage which prevents the invasion of blood vessels. Appropri- ately, this factor has been named the anti-ineasion factor (ALF). By an unknown mechanisin, calcification of cartilage must inactivate ALP, permitting a vascular bud to penetrate the iniddle of the shalt. This bud eventually becomes the inajor Lloud supply to the bone, the nutrient artery This vascular ingrowth brings with it stromal cells which apparently have the potential to differentiate into osteogenic, endothelial, reticular, and possi- bly other cell lines. Trabeculation and the appearance of the sinusoidal mi- pole crocirculation appears to be necessary for seeding of the marrow by hemo- poictic cells from the yolk sac or fetal liver. ‘The osteogenic cells of the marrow stroma differentiate into osteoblasts and osteoclasts, which begin to convert the cartilage to bone. In this process the calcifying froats of cartilage, followed2200 ASYNOPSIS OF CRANIOFACIAL GROWTH closely by the zones of conversion, spread rapidly from the middle toward both the proximal and distal ends of the bone. In the zones of conversion, cartilage is selectively resorbed, and spicules are left as sites for osteoblast attachment. Osteoid is deposited around these cores of calcified cartilage, remodeling oc- curs, and the trabecular pattern of spongy bone is soon established. At the periphery of the shaft, cortical bone is formed. The fronts becomes stationary short of the ends, leaving the heads as cartilage. The zone of conversion becomes the forerunner of the growth plate and begins to contribute to linear growth (Fig. 1-9). It does this by directed cartilage proliferation and replacement by bone. In this manner, the heads of the bone are displaced away from each other as the shaft lengthens. The classic growth plate does not appear until the cartilage heads are invaded by separate blood supplies and converted to osseous tissue. Asa result, a section of cartilage is left sandwiched between bony compartments at each end of the bone; these remnants, called growth or epiphyseal plates, are responsible for all future linear growth. The very ends of the bone remain as articular cartilage. The pattern of cells in the anlage changes, then, from a random state to one highly organized and directed. The cells align themselves in longitudinal col- umns which are maintained through the width of the plate. Beneath the reserve cartilage layer, cells of the proliferating zone synchronously divide and secrete matrix. This has the effect of lifting the head of the bone away from the shaft as the plate thickens. The cartilage cells in the growth plate are not supplied by ARTICULAR CARTILAGE GROWTH PLATE DEGENERATIVE OR ZONE OF HYPERTROPHY ‘CALCIFICATION BONE FORMATION Figure 1-9. The zones of cells in the growth plate that are responsible for the conversion of cartilage to bone.>) BIOLOGY OF THE SUPPORTING TISSUES 23 blood vessels, however, and they must rely on perfusion for their needs. Conse- quently, the older cells below them become more removed from tissue fluid, presumably initiating a transition into cell death and calcification. From the metaphyseal side, vascular buds invade this newly calcified cartilage and con- vert it to bone. The columnar pattern established in the zone of proliferation is crucial to the conversion, since it delineates the cores of calcified cartilage to be used as support for osteogenesis. The process of cartilage formation on one side and bony replacement on the other maintains the epiphyseal plate at a constant thickness during growth. The plates stay active through puberty, after which they are transformed to bone under the influence of sex hormones. The active separation of tissues against a load is characteristic of endo- chondral growth. The growth plate and other bone-forming areas with similar properties are called growth centers, a term introduced by Baume. Diametri- cally opposed to the autonomous nature of growth centers is the adaptive, passive nature of other osteogenic areas. In these situations, new bone is formed only as an aftermath of bone separation instigated by other forces. Such locations are known as growth sites; sutures are often cited as examples. Spheno-occipital synchondrosis. The structure in the skull most resembling the growth plates of long bones is the cartilage remnant located between the sphenoid bone and the occipital along the midline of the cranial base (Fig. 1- 10). Its cellular organization suggests the appearance that one might get by butting together two growth plates with the reserve cartilage layers back to back. As a result of this architecture, interstitial expansion is bidirectional, increasing the size of bones simultaneously. This joint is a true sychondrosis, being totally replaced by bone shortly after puberty. Because the spheno-occipital synchondrosis looks like two growth plates back to back, it has been tempting to classify it as a growth center capable of independent tissue separation. However, experiments comparing the growth of both transplanted synchondroses and growth plates have indicated that the latter structure possesses more potential for autonomous growth. This suggests that part of the impetus for complete synchondrotic growth may arise from brain growth. To date, the question concerning the autonomous or adaptive nature of this joint has not been resolved OCCIPITAL 'SYNCHONDROSIS Figure 1-10. The spheno-occipital synchondrosis, situated between the sphenoid and occipital bones at the midline of the cranial floor.2400 ASYNOPSISOF CRANIOFACIAL GROWTH Nasal cartilage. The nasal septum seen in the adult skull divides the nasal cavity into two parts (Fig. 1-11). It runs vertically in the midline of the face from the ethmoid and sphenoid above to the v below. This septum is initially formed entirely of cartilage, but in the adult all of it is converted into bone save the anterior segment which unites with the soft tissue of the nostril. The advancing bone tissue sweeps diagonally across the cartilage, downward and forward (Fig. 1-12). The cartilage of the nasal septum is presumably capable of interstitial expansion, and because the vertical size of the nasal cavity increases so dramati- cally during growth, much speculation has naturally arisen about the role of the asal cartilage in the process. Generalized division of chondrocytes and matrix production and/or regional mitosis and synthesis along the zone of conversion could create a tissue-separating force that could propel the maxilla and contigu- ous bones downward and forward. Latham has described in prenatal develop- ment a septomaxillary ligament which links the septum to the anterior maxilla. Theoretically, this attachment could enable the enlarging septum to “drag” the maxilla forward. Whether this ligament persists and plays a role in ‘postnatal growth is unknown. If the nasal cartilage did in fact generate this kind of force, it could be classified as a growth center. Unfortunately, experiments designed to test the PERPENDICULAR PLATE GRIBRIFORM PLATE ‘NASAL CARTILAGE Figure 1-11. Cross section of the midface showing the relationship of the nasal cartilage to the floor of the cranium (top) and the vomer and maxilla (bottom) (Adapted from Scott JH: Dento-tacial Development and Growth. Oxford, Perga- mon Press, 1967.)BIOLOGY OF THE SUPPORTING TISSUES 25 Figure 1-12. A midsagittal section showing the anatomic relationship of the nasal cart lage to the cranial base and the maxilla role of the nasal cartilage have been equivocal, and its clear-cut desig ation as a growth center, growth sit or something in between, has not been possible. Condyle. In the long bone, the load-bearing surface, the articular cartilage, is separated from the cartilage growth zone by epiphyseal bone. In the condyle, on the other hand, the articular surface and the cartilage replacement tissue are juxtaposed (Fig. 1-13). In addition, their histologic character and source of cellular replenishment are unlike those found at any other site FIBROUS Figure 1-13. The head of the condyle showing the unique arrangement of tissues and cells.26 ASYNOPSIS OF CRANIOFACIAL GROWTH Most of the articular surfaces of long bones are cartilage with no peri- chondrium. Articular cartilage has an ability to expand interstitially as a result of cell divisions only in the young. The mature articular matrix is sustained by the chondrocytes, but there is little capacity to compensate for functional wear and tear. In contrast, the articular surface of the condyle is not baré cartilage but rather fibrous tissue (sce Fig. 1-13). Immediately subjacent to this fibrous layer is a zone of mesenchymal cells capable of two functions. First, they can secrete the elements of the peripheral fibrous layer and, second, they can differentiate into cartilage cells to replenish those lost in the conversion to bone. The latter Process occurs in a direction opposite to the former. Thus, in the condyle, a replacement mechanism is operating during growth that differs from other areas both in the source of new cartilage and in the orientation they aysume. In the condyle, new cartilage cells are derived from noneartilage precursors; in all other replacement mechanisins, new carti- lage cells are derived from other cartilage cells by division. Petrovic has claimed that the prechondroblasts or noncartilage precursor cells of the condyle (cells not yet surrounded by cartilaginous matrix) have the same ancestry as pre- osteoblasts of bone tissue. He has given the name “skeletoblast” to the pur- ported stem cell which can differentiate either into a condylar chondroblast or a bone osteoblast. ie The cells of the cartilage of the condyle remain haphazard, random, or embryonic; they do not form the specialized columnar arrangement of the growth plate. The cartilage replacement system of the condyle does mature, however. The hypertrophic cells disappear, the width of the cartilage dimin- ishes, and the junction between cartilage and bone becomes well demarcated. Cartilage, unlike the growth plate, is never completely eliminated; the mature condylar cartilage can even be reawakened by growth hormone. This unique feature of the condyle is demonstrated by mandibular overgrowth of the acromegalic. At least one authority has speculated that the unique character of the condyle is not so much a genetically enforced structure as it is an adaptation of the periosteum to load. Such a theory implies that periosteal pluriopotential cells (skeletoblasts?) can revert to chondrocytes in vivo as they have been shown to do in tissue culture. Pressure on the articular surface of the condyle would cause dedifferentiation of the periosteal cells and result in the formation of a semifibrous-semicartilage covering. Whether such a concept has any validity remains to be answered, but without question, the condyle is unique as a cartilage replacement mechanism. INTERNAL REMODELING OF BONE The previous section dealt with those mechanisms that were concer ‘ned ce with the development of size. Descriptions of remodeling processes whi ne establish the shape of bones (and which occur concurrently with growth) wit pe discussed in Chapters 2, 3, 4, 5, and 7. The morphology of bone, as described byBIOLOGY OF THE SUPPORTING TISSUES, 27 the size and shape, is limited by maturation; during puberty or shortly thereafter, our maximum size is attained and our bones no longer grow. They do not cease to change, however. The development of their internal architecture or structure, begun almost as soon as bone is formed, continues throughout life in response to the changes in stress on them. For instance, ifwe were to acquire a middle-age spread, our bones would adapt to the added load. ‘Thus, there is an internal remodeling of bone which is not related to external form; compact and cancellous bone, however, exhibit completely different approaches to the process. Compact Bone Internal remodeling of cortical bone involves the development of haversian systems, which consist of multiple cylinders of new bone with a vascular core. These cylinders in primary vascular bone, primary osteons, have already been described. In mature cortical bone, the ostcons cannot be established by sur- face envelopment of blood vessels; instead, they must be created in tunnels bored by osteoclasts. These osteons, called secondary osteons because they develop after the shaft is formed, represent redeposition of osseous tissue within hollow cylinders (Fig. 1-6).On cross section, the cortex of bone exhibits empty circles where only the resorptive phase has occurred, and others where incremental and centripetally directed apposition has followed. The transition from empty tunnels to cylinders of bone is not an all-or-nothing phenomenom, that is, the entire tunnel is not resorbed at one time followed by circumferential apposition throughout its entire length. Instead, the resorption-apposition pro- cess is sequential or linked; as osteoclasts burrow through the cortex, trailing osteoblasts fill in behind. The unit has been described as a cutting cone. What remains after these cones move through the cortex are cores of new bone up to 250 um in diameter and 5000 um in length that house blood vessels in their centers. The secondary osteons ensure a blood supply to osteocytes within the cylinder, and they permit adaptation to new stresses by the appropri- ate reorientation of cortical bone. A clever way, indeed, to restructure a dense mass without external changes. Cancellous bone. The internal cavities of most bones have a porous arrange- ment of interconnecting trabeculae which houses marrow (sce Fig. 1-3). In addition to this highly important function, the trabeculae are critical structural elements of bone. They are oriented, particularly at the ends of bone, in pat- terns that support the cortices in the bearing of loads, The trabeculae are situated much like supporting beams of a bridge or tower; they are directed to beot resist stresses, providing maximum support with minimum weight. In fact, it was observations made on the cancellous portions of dried, longitudinally halved bones that led to the concept that much of the internal form of bone is an adaption to function. This association has been formalized into what has become known as Wolll’s law. This law maintains that a bone’s morphology progres- sively adapts to the changing mechanical focus which act upon it during growth and development The dividing line between compact and spongy bone is by no means immuta28 A SYNOPSIS OF CRANIOFACIAL GROWTH ble; during the remodeling associated with growth and development there is considerable conversion of one to the other. Thus, superimposed on the internal remodeling (development of the haversian system and adaption of the trabec- ulae), is the external remodeling associated with growth and the osteocytic osteolysis associated with calcium metabolism. One comes to appreciate quickly the many activities of bone tissuc. ORIGIN OF THE CARTILAGE REPLACEMENT MECHANISMS OF THE HEAD Chondrocranium Most of the bones associated with the floor of the cranium and the cranial base begin their existence as cartilage. During embryologic development, areas around the notochord begin to chondrify, and eventually most of the occipital, the petromastoid portions of the temporals, the majority of the sphenoid, and a great deal of the nasal area including the ethmoid are aggregated into a cartilaginous complex called the chondrocranium. This structure is fairly well defined by day 51 [18 to 22 mm crown-rump length] of prenatal development, and by day 57 has developed into a continuous craniofacial skeleton. At birth, very little of this primordial cartilage remains, having been con- verted into bone. The junctions between these cartilaginous structures, and between them and membrane bones, are for the most part demarcated by sutures. Two prominent exceptions to the complete postnatal elimination of cartilage are the spheno-occipital synchondrosis and the nasal cartilage. Spheno-occipital Synchondrosis The sphenoid bone consists of a central body and lateral Sreater and lesser wings. The body is divided embryologically into a presphenoid segment (that which is anterior to the tuberculum sellae) and the postsphenoid segment, comprising the sella turcica and dorsum sellae (Fig. 1-14), These two parts fuse by 8 months of fetal life. Posterior to the postsphenoid, the cartilage of the basilar part of the occipital bone becomes ossified simultaneously, Both the postsphenoid and basilar occipitals continue ossification until all that remains is a plate of cartilage between them, the spheno-occipital synchondrosis. This IN UTERO POSTNATAL Figure 1-14. The formation of the spheno-occipital synchondrosis following ossiti- cation of the original chondrocranium.BIOLOGY OF THE SUPPORTING TISSUES, 29 area is responsible for most of the lengthening between the foramen magnum and sella turcica, a process that continues until fusion of the sphenoid and occipital bones during the latter halfof the sccond decade of life. Nasal Cartilage The embryologie nasal capsule develops into the ethmoid bone and the inferior nasal conchae (see Fig. 1-11). The ethmoid bone consists of a horizontal or cribriform plate, which forms a part of the cranial base; a perpendicular plate, constituting part of the nasal septum; and two lateral masses or labyrinths. The perpendicular plate and the christa galli of the cribriform begin to ossify, form- ing a single center during the first year after birth. Ossification continues until they join the already ossified labyrinths sometime during the second year. At this time, a septum with potential tissue-separating force is buttressed posteri- orly against the sphenoid and superiorly against the cribriform plate, just oppo- site to an anterior and inferior articulation with the vomer. This arrangement makes it easy to visualize a downward and forward thrust of the maxillary complex as a result of nasal cartilage expansion Splanchnocranium-condylar Cartilage The maxilla and mandible, intramembranous bone branchial arch. The maxilla has no cartilage precursor whatsoever, but the mandible develops membrane bone lateral to a temporary structure called Meckel’s cartilage (Fig. 1-15). By 6 weeks of development, the primitive mandi- ble is supported by two solid cartilaginous rods which extend from the areas of the future ear to the midline of the fused mandibular processes. At 7 weeks, intramembranous ossification begins lateral to these rods at sites near the men- tal foramen. The process of ossification spreads anteriorly and posteriorly. The antcrior ossifying segments remain separate at the symphysis until shortly after mainder of the body of the mandible are derived from the first h. Posterior ossification forms the r and a partial ramus which is devoid of a condyle and coronoid process c ‘ORONO i CONDYLE, = - LIGAMENTS DEVELOPMENT OF THE MANDIBLE Figure 1-15. The relationship of Meckel’s cartilage to the membrane bone and the secondary cartilage of the coronoid and condylar processes30 ASYNOPSIS OF CRANIOFACIAL GROWTH The cartilage that is found in the condyle, and which is responsible for long-term growth of the mandible lated to the first brancial arch (Me is derived from mesenchymal cells unre- I's) or the chondrocranium. It is often referred to as a s¢ cartilage, since the formation is secondary to the original primordial ge. Developmentally, the secondary cartilages of the mandible include coronoid and symphyseal components as well. The condylar cartilage appears asa cone or carrot-shaped mass in the ramus during the 12th week of development; the large end assumes the position of the future condyle. By the 20th week this wedge of cartilage is converted to bone save for a thin layer at the articular surface. It is interesting that in certain deficiency states, the condylar cartilage reverts to a wedge shape. This rever- sion supports other evidence which suggests that condylar cartilage is unique. In fact, Durkin and colleagues suggest that the term secondary has little descrip- tive value and should be replaced with embryonic, since the organization and growth of the cartilage cells of the condyle resemble the anlages of long bones more than specialized growth plates. The cartilage that serves as a precursor of the coronoid Process appears at about 4 months of development and is converted to bone before birth. The paired symphyscal cartilages that form mesial to, but separate from, Meckel's cartilage are less transient, persisting into the first postnatal year. These symphyseal cartilages presumably aid in lateral growth at the midline, an activ- ity required for proper alignment of primary incisors. BIBLIOGRAPHY Babula WJ, Smiley GR, Dixon AD: ‘The role of cart growth. Am J Orthod 58:250, 1970 Baume, LJ: Principles of cephalofacial development revealed by experimental biology. Am J Orthod 47:881, 1961. Bonucei E: New knowledge on the origin, function and fate of osteoclasts. Clin Orthop 158:252, 1981. Caplan Al: Cartilage. Sci Amer 251(4):54, 1984. ; Durkin JF, Heeley JD, Irving JT: The cartilage of the mandibular condyle. Oral Sci Rew 2:29, 1973. Enlow DH: Handbook of Facial Growth. Philadelphia, Saunders, 1975, Hall BK (cd): Cartilage, Vols 1 and 2. New York, Academic Press, 1983. . Ham AW, Cormack, DH: Histology, 8th ed. Philadelphia, Lippincott, 1979. Latham RA: Maxillary development and growth: the septo-premaxillary ligament. J Anat 107:471, 1970. . Miller EJ: Recent information on th nistry of the collagens. in batter t . wh Chemistry and Biology of Mincralized Tissues. Birmingham, Ala., Ebsco Media, ate Ae Slruelureand sot of facil sts. Odont Hew 248uppl 20) 1973. Petrovic A: Postnatal growth of bone: a perspective of current trends, new barieaceat and innovations. In Dixon AD, Sarnat BC (eds): Factors and Mechanisms In} Bone Growth, Prog Clin Biol Res 101:297, 1982. aginous nasal septum in midfacialBIOLOGY OF THE SUPPORTING TISSUES 31 Ranly DM: Bone apposition and resorption, In Lazzari EP (ed): Dental Biochemistry, 2nd ed. Philadelphia, Lea & Febiger, 1976, p 134. Rubin, P: Dynamic Classification of Bone Dysplasias. Chicago, Year Book Medical, 1964. Scott JH: The cartilage of nasal septum. Br Dent J 95:37, 1953. Urist MR, Conover MA, Lietze A, Finerman GAM: Dentin, bone, and osteosarcoma tissue bone morphogenetic proteins. In Dixon AD, Sarnat BG (eds): Factors and Mechanisms Influencing Bone Growth. New York, Alan R. Liss, 1982, pél. Weinman JP, Sicher H: Bone and Bones; Fundamentals of Bone Biology, 2nd ed. St. Louis, Mosby, 1955. Yasui N, Ono K, Konomi H, Nagai Y: Transitions in collagen types during endochondral ossification in human growth cartilage. Clin Orthop 183:215, 1984,