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3American Academy of Orthopaedic Surgeons
Articular Cartilage
Structure and Function
Similar to other connective tissues, articular cartilage consistsof cells (chondrocytes), water, and an extracellular matrix(ECM) framework from which it derives its form andmechanical properties. Despite its lack of blood vessels, lym-phatic vessels, and nerves, detailed study of the morphologyand biology of articular cartilage shows that it has an elabo-rate, highly ordered structure and that multiple complexinteractions between the chondrocytes and the matricesactively maintain tissue balance.Chondrocytes from different cartilage zones differ in size,shape, and metabolic activity, but all cells contain the require-ments for matrix synthesis. They frequently contain intracy-toplasmic filaments as well as short cilia extending from thecell into the matrix. These structures may have a role in sens-ing mechanical changes in the immediate surrounding envi-ronment. Individual chondrocytes are very active meta- -bolically in the homeostasis of their surrounding matrix. Theyderive their nutrition from nutrients in the synovial fluid,which must pass through a dou-ble diffusion barrier: first the tis-sue and synovial fluid, and thenthe cartilage matrix.The ECM consists primarily of water (65% to 80% of its total wetweight), proteoglycans, and collagen. The predominant colla-gen is type II (95%), but smaller amounts of other collagens(types IV, VI, IX, X, XI) also have been identified. The func-tions of the remaining types of collagen are under investiga-tion. Types IX and XI may help form and stabilize the colla-gen fibrils assembled primarily from type II collagen. Type VImay form an important part of the matrix immediately sur-rounding the chondrocyte and assist with matrix attachment.The interaction of these substances gives articular cartilage itsmechanical properties. The aggrecan proteoglycan moleculecomprises many glycosaminoglycan chains (keratan sulfateand chondroitin sulfate) that contain numerous charged car-boxyl and sulfate groups. The organization of these aggrecanswithin the collagen framework produces a strong, cohesivecollagen-proteoglycan solid matrix. The proteoglycans withtheir predominate negative charge and counterions areresponsible for the water content of the articular cartilage,which has a direct influence on its deformational properties.Articular cartilage has a highly organized tissue structureand can be divided into 4 distinct zones (Fig. 1). It is arrangedin layers of differing morphology and biochemical composi-
Orthopaedic Knowledge Update
Chapter 1
Soft-Tissue Physiologyand Repair
Figure 1
Structure of articular cartilage. (Reproduced withpermission from Buckwalter JA, Mow VC,Ratcliffe A: Restoration of injured and degenerat-ed articular cartilage.
J Am Acad Orthop Surg 
The Articular Cartilage section of this chapter has been adapted from Buckwalter JA, Mankin HJ: Articular cartilage:Tissue design and chrondrocyte matrix interactions, in Cannon WD Jr (ed):
 Instructional Course Lectures 47 
.Rosemont, IL, American Academy of Orthopaedic Surgeons, 1998, p 477–486.
Superficial tangentialzone
tion, with mechanical properties varying according to thedistance of the layer from the joint surface. The homeostasisbetween chondrocytes, water, collagen, ultrastructural archi-tecture, and proteoglycans dictates the tensile stiffness andstrengths of each zone. From the superficial to deep zones,sheer stress increases while tensile stiffness decreases. Thesuperficial zone contains chondrocytes that synthesize amatrix that has a high concentration of collagen and a lowconcentration of proteoglycan. The parallel arrangement of the collagen fibrils in this zone provides greater tensile stiff-ness and strength than in the deeper zones, and this may helpresist shear forces generated during use of the joint. The mid-dle (transition) zone has a morphologic and matrix compo-sition in between that of the superficial and deep zones andcomprises the largest part (40% to 60%) of the articular car-tilage. The deep (radial) zone has the largest-diameter colla-gen fibrils, the highest concentration of proteoglycans, andthe lowest concentration of water. The collagen fibrils passinto the tidemark, a thin basophilic line seen on lightmicroscopy sections of decalcified articular cartilage thatroughly corresponds to the boundary between calcified anduncalcified cartilage. Shear stresses are greatest at the tide-mark. A zone of calcified cartilage separates the radial zonefrom the subchondral bone. The cells of this zone have a verysmall volume and appear to be surrounded completely bycalcified cartilage. Recent work suggests that they may have arole in the development and progression of osteoarthrosis.
Biomechanics and Physiology
Articular cartilage exhibits a time-dependent behavior (vis-coelastic) when subjected to a constant load or constantdeformation. When a constant compressive stress (load/area)is applied to the tissue, its deformation will increase withtime, that is, it will creep until an equilibrium value isreached. Similarly, when the tissue is deformed and held at aconstant strain, the stress will rise to a peak, followed by aslow stress-relaxation process until an equilibrium value isreached. Two mechanisms are responsible for viscoelasticity:a flow-independent and a flow-dependent mechanism.During walking or running, articular cartilage is subjectedto compressive forces that rise to several times body weightwithin a very short period of time. Under this dynamic load-ing environment, interstitial fluid trapped within the carti-lage matrix enables the tissue to resist these high compressiveforces without mechanical damage. The instantaneousincreased hydrostatic pressure will be sustained within thetissue matrix for an extended period of time. When the inter-stitial fluid flows through the dense matrix, a frictional inter-action between the fluid and the matrix is created, providinga mechanism for energy dissipation. This phenomenon, theflow-dependent biphasic viscoelasticity of articular cartilage,provides additional protection of the tissue matrix frommechanical damage. Independent of the interstitial fluidflow, the proteoglycan molecules and the collagen fibersthemselves have shown significant viscoelastic characteris-tics. Thus, the cartilage matrix constitutes the intrinsic vis-coelasticity in shear deformation. This second phenomenonis called flow-independent intrinsic viscoelasticity, and hasbeen shown to significantly govern the short-term behaviorof articular cartilage immediately after a mechanical load isapplied to the tissue, such as in running or walking.Joint loading and motion are required to maintain normaladult articular cartilage. Immobilization of a joint will causea rapid loss of proteoglycans from the cartilage matrix.Proteoglycan content is affected to a greater extent than col-lagen composition. Because proteoglycan is lost, fluid fluxand deformation in response to compression will increase.Tensile properties, which depend primarily on collagen, aremaintained. These biochemical and biomechanical changesare, at least in part, reversible with the restoration of motion.The extent of recovery decreases with increasing periods of immobilization.Increased joint loading, either through excessive use orincreased magnitudes of loading, will also affect articular car-tilage. Disruption of the intra-articular structures, such asmenisci or ligaments, will alter forces acting on the articularsurface. In experimental animal models, responses to tran-section of the anterior cruciate ligament (ACL) or meniscec-tomy have included fibrillation of the cartilage surface,increased hydration, and changes in proteoglycan content.Significant and progressive decreases in the tensile and shearmodulus have been observed in response to transection of the ACL.While the overall metabolic activity of articular cartilage islow, the activity surrounding each individual chondrocyteand surrounding ECM is quite dynamic. This activity isdetermined by a cellular response to soluble mediators(nutrients, growth factors, cytokines), mechanical loads,matrix composition, hydrostatic pressure changes, and elec-tric fields. Growth factors, such as insulin-like growth factor-I and transforming growth factor-
), may stimulatematrix synthesis and cell proliferation. Chondrocytes synthe-size and release these growth factors, which further enhancethe metabolic activity of chondrocytes and matrix produc-tion. Matrix catabolism is mediated by enzymes, includingstromelysin, aggrecanase, and collagenase, which are regulat-ed in a complex manner by local factors such as interleukin-1 (IL-1), prostaglandins, TFG-
, tumor necrosis factor, andother molecules.The ECM is known to act as a signal transducer for the
4General KnowledgeAmerican Academy of Orthopaedic Surgeons
Orthopaedic Knowledge Update
Soft-Tissue Physiology and Repair5
chondrocytes and may transmit signals that result frommechanical loading of the articular surface to the chondro-cytes. The chondrocytes respond to these signals by alteringthe matrix, possibly through the expression of cytokines thatact through local factors. It has been shown that a persistentabnormal change in joint loading or immobilization of a joint may change the concentration of proteoglycans in artic-ular cartilage and the degree of proteoglycan aggregation thatalters the mechanical properties of cartilage. The exact detailsof how the mechanical loading of joints influences the func-tions of chondrocytes remains investigational, but deforma-tion of the matrix produces mechanical, electrical, and phys-iochemical signals that may have major roles in stimulatingchondrocytes.
Articular Cartilage Injury
Mechanical injuries to articular cartilage can be separatedinto 3 distinct types: (1) microscopic damage to the chon-drocytes and ECM without visible disruption of the articularcartilage surface, (2) macrodisruption of the articular carti-lage alone (chondral fracture), and (3) osteochondral frac-ture or disruption of the articular cartilage and subchondralbone.Microscopic injury may result from a single traumatic eventor multiple repetitive loads. A reliable method of detectingdamage to articular cartilage in the absence of surface dis-ruption (ie, chondral fracture) has yet to be developed. Thismicroscopic mechanism most likely results in damage to thechondrocytes and affects their ability to produce collagen andproteoglycans. The point at which the accumulated micro-damage becomes irreversible is unknown. Chondrocyteshave the ability to restore lost proteoglycans if the rate of lossdoes not exceed the rate of production. If there is concomi-tant damage to the collagen ultrastructural architecture or if a sufficient number of chondrocytes have been damaged, anirreversible degeneration process may ensue. Although theexact natural history of this type of damage is still beingdefined, the decrease in proteoglycan concentration, theincrease in tissue hydration, and disorganization of the artic-ular cartilage is worrisome.Clinically, this scenario has been observed in conjunctionwith knee ligament injuries. After an ACL injury to the knee,an occult osteochondral lesion or “bone bruise” may bedetected in up to 80% of patients by magnetic resonanceimaging (MRI). The most common location of these lesionsis within the lateral compartment of the knee, on the lateralfemoral condyle at the sulcus terminalis, and the posterolat-eral tibial plateau. Although the area may appear normal dur-ing arthroscopic examination, recent in vivo histologic stud-ies have shown a significant disruption of the articularcartilage. The reversiblity of these chondral injuries is stillbeing debated. It is hoped that ongoing clinical and basic sci-ence studies will provide the clinician with new scientificinformation on the natural history and optimal treatment of these injuries.Isolated partial and full-thickness articular cartilage injuries(chondral fractures) are often problematic because of thelimited blood supply. This relatively poor blood supply (incomparison to bony injuries where a vascular response isrobust) combined with the isolated environment of thechondrocyte makes the potential healing of articular cartilagepoor. For smaller lesions (< 1 cm in size), overall joint home-ostasis may not be affected; however, as the lesion increases insize, overall joint congruity is affected, resulting in increasedloading of the immediately adjacent articular cartilage andsubchondral bone. Over time, the remaining healthy articu-lar cartilage may be affected, eventually leading to moreincongruity and damage.With increasing force, the depth of the injury may extendbeyond the articular cartilage into the subchondral bone,resulting in an osteochondral injury. These injuries, whichcross the tidemark, cause hemorrhage and clot formation,thereby activating the inflammatory cascade. This type of injury has many biologic differences from a pure chondralinjury. Blood products within the fibrin clot release vasoac-tive mediators and growth factors or cytokines. These factorsmay stimulate vascular invasion and migration of undiffer-entiated cells, which may play an important role in stimulat-ing repair of this injury. The undifferentiated mesenchymalcells that migrate into the chondral portion of the defect pro-duce a repair cartilage that has a combination of types II andI collagen. The cells in the osseous portion of the defect even-tually produce immature bone that is gradually replaced bymature bone.The composition of this repair tissue rarely replicates thestructure of the normal articular cartilage and subchondralbone. The subchondral portion of the defect is filled withregions of fibrous tissue and hyaline cartilage. The composi-tion and structure of the chondral repair tissue are interme-diate between those of hyaline cartilage and fibrocartilage.The inferior material properties of this repair tissue withinthe defect make it more susceptible to injury under physio-logic loading conditions.
Numerous methods exist to replace or regenerate articularcartilage. The efficacy of all current techniques is still beingevaluated by basic science research and clinical trials.Depending on the location and depth of the lesion (Fig. 2),different techniques may be used. Pure chondral injuries can
American Academy of Orthopaedic Surgeons
Orthopaedic Knowledge Update

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