Introduction Classification Composition Histology Bone formation Bone turnover Bone remodeling

Bones

are calcified connective tissue forming the major portion of the skeleton of most vertebrates more calcium than any other organ consists of a dense organic matrix and an inorganic, mineral component

Functions of the bone in brief;

toughness

and elasticity shape and support site of attachment for tendons and muscles Protects vital organs of the body Serve as a storage site for minerals provides medium for development and storage of blood cells marrow

 Bones

may be classified according;

Shape. of development.

Mode

Histologic appearance.

 Classification
Long

based on shape:

bones. Flat bones. Irregular bones.

They are long and slender. Longer than wider.

Cube shaped of nearly equal length and width. Consists of spongy bone covered by thin layer of compact bone. Examples; bones of wrist and ankle.

Thin, flat ,curved with no marrow cavity. spongy bone is present between upper and lower layer of compact bone. Examples;

sternum,ribs,clavicle

Have complex shapes, notched or with ridges. Made of spongy bone covered with layer of compact bone. Examples; vertebrae,mandible, sphenoid,pelvic bones.

Endochondral bones

Bones of trunk and extremities

Intramembranous bones

Cranial and facial flat bones of the skull, mandible and clavicles.

Histologically; Two types;

Mature bone Immature bone

Mature bone Two types compact (cortical) bone cancellous(spongy) bone

 Woven/immature

bone.

First formed bone with irregularly oriented collagen fibers of varying diameter. Present in
alveolar

bone healing of fractures.

67%

33%

inorganic

organic

hydroxyapatite 28%

5%

collagen

Osteocalcin Sialoprotein Phophoprotein Osteonectin Bone specific protein

The mineral component; hydroxyapatite thin plates or leaf like structures packed closely with long axis nearly parallel to collagen fibril axis
The narrow gaps between the crystals contain water and organic macromolecules. Ions present; Carbonate,calcium phosphate,hydroxyl.

5% of the total organic content of bone matrix. Endogenous proteins produced by the bone cells. Albumin is derived from the blood and become incorporated into the bone matrix during osteosynthesis.

Osteocalcin; noncollagenous protein 15% of the noncollagenous bone protein. Also known as bone Gla protein Aminoacid gamma carboxy glutamic acid.

Regulation by vitamin D and parathyroid hormone.

 Osteopontin

and bone sialoprotein ;

heavily glycosylated and phosphorylated high levels of acidic aminoacids

osteopontin sialoprotein

Aspartate Potent inhibitor of hydroxy apatite crystal growth. Transcription is upregulated by vitamin D3

Glutamic acid Plays role in the intiation of mineral crystal formation. suppressed by vitamin D3

Osteonectin
25% of noncollagenous proteins bound to hydroxyapatite crystal regulation of cell adhesion proliferation and modulation of cytokine activity

Proteoglycans
A large chondroitin sulphate proteoglycans Non mineralized bone matrix Small proteoglycans, biglycan and decorin(<10%) EDTA extracts of bone

Others
Lysyl oxidase(collagen cross linking) and tyrosine rich acidic matrix protein(TRAMP) Demineralised bone and bone matrix

TRAMP( dermatopontin) binds decorin and TGF-beta Regulate the cellular response to TGF beta

Dense outer sheet of compact bone and a central medullary cavity Cavity is filled with red or yellow bone marrow interrupted, particularly at the ends of long bones, by a network of bone trabeculae ie.trabecular, cancellous, or spongy bone

Circumferential lamellae;
At the periosteal and endosteal surfaces, the lamellae in parallel layers surrounding the bony surface

Concentric lamellae;
Deep to the circumferential lamellae, the lamellae are arranged in concentric layers around a central vascular canal

Interstitial lamellae: are interspersed between adjacent concentric lamellae and fill the spaces between them

Red marrow

young bone

yellow marrow

old bone

osteoblasts

osteocytes

osteoclast

mononucleated cells synthesis and secretion of macromolecular organic constituents of bone matrix osteoprogenitor cells of mesenchymal origin

Osteoblasts

undifferentiated pluripotent stromal stem cells

differentiate into inducible osteoprogenitor cells(IOPCS) IOPCs

Determined osteoprogenitor cells(DOPCS)

osteoblast

Osteoblasts

Formation of new bone via synthesis of various proteins and polysaccharides Regulation of bone remoldeling and mineral metabolism In the mineralization of osteoid

Osteoblasts

Bone resorbing factors

parathyroid hormone, vitamin D3,interleukin1 tumor necrosis factor

Receptor for these bone resorbing agents Recognize the resorptive signal and transmit it to the osteoclast

Osteoblasts

The overall integrity of bone is controlled by;

Hormones Protein secreted by hematopoietic bone marrow cells Bone cells

Osteoblasts

In response of hypocalcemia; hormone activates the mechanism for the release of calcium from the bone

PTH does so; indirect effect mediated by PTH receptors on bone stromal cells including osteoblast

Osteoblasts

Stimulates bone resorption Essential for normal bone growth and mineralisation Promotes calcium absorption from the intestine

stimulates synthesis of osteocalcin and osteopontin by osteoblast

suppresses collagen production

Osteoblasts

Parathormone and vitamin D3 enhance; bone resorption at high concentration(pharmacological) bone formation at low(physiological)

Osteoblasts

Required for attaining normal bone mass; Mediated by the local production of IGF-1 Binds to membrane growth hormone receptors on activated osteoblast

Osteoblasts

It targets osteoblast directly Stimulates bone matrix formation Mineralisation Indirectly affects bone formation through stimulation of IGF-1

Osteoblasts

Formation of new bone including; Migration Aggregation Proliferation of mesenchymal type cells Differentiation into osteogenic cells

Osteoblasts after, completing their function got entrapped in bone matrix and become osteocytes or remain on the surface as the lining cells

Osteoblasts form the bone matrix, they got entrapped within the matrix they secrete and are called as osteocytes The number of osteoblasts that become osteocytes, depend on the rapidity of bone formation

Osteocytes

Osteocytic lacunae;
within the bone matrix, the osteocyte reduce in size creating a space around it ovoid or flattened

Osteocytes

Narrow extensions of these lacunae forms channels called canaliculi Osteocytic processes are present within these canaliculi; contain bundles of microfilaments and smooth endoplasmic reticulum.

 At

the distal end, these processes contact the processes of adjacent cells(osteocytes) contact with osteoblasts and bone lining cells at the surface

The word osteoblast is derived from the Greek words for bone and broken Removes bone tissue by removing the mineralized matrix of bone

Osteoclasts

Osteoclasts lie in resorption bays called Howships lacunae. large cell approximately 40-100m in diameter with 15 to 20 closely packed nuclei. multinucleated osteoclast resorb more bone than with few nuclei.

Osteoclasts

The cytoplasm also microtubles which transport vesicles between golgi stacks and ruffled membrane

Cathepsin containing vesicles and vacuoles are present close to the ruffled border indicating resorptive activity of these cells

Osteoclasts

Haemopoietic cells of monocyte macrophage lineage Proliferate and differentiate into osteoclasts through a mechanism involving cell-cell interaction with osteoclast stromal cells

Osteoclasts

The formation requires the presence of RANK ligand and M-CSF

Neighboring stromal cells and osteoclast precursor

RANK Ligand and M-CSF

Osteoclasts

RANKL; Differentiation into mature osteoclast osteoclast activity

RANK is expressed by osteoclast precursors, a membrane bound TNF receptor that recognizes RANKL through direct cell to cell interaction with osteoblast or stromal cells

Osteoclasts

The soluble TNF receptor family member OPG is a natural RANKL antagonist ; inhibit osteoclast formation and bone resorption. Estrogen suppresses the ; production of bone resorbing cytokines including IL-1 and IL-6.

Osteoclasts

Calcitonin

inhibits; proliferation differentiation of osteoclast precursors reduces the dimension of ruffled border and dissociation into monocytic cells

 Three

mechanisms

Endochondral bone growth

Intramembranous bone growth

Sutural bone growth

Take place when the cartilage is replaced by bone. Site;

At the ends of long bones Vertebrae Ribs Head of the mandible Base of the skull

Mesenchymal cells

condenses and differentiate into chonbroblast

cartilage matrix(hyaline cartilage model)

 Hyaline

cartilage model is surrounded by perichondrium

Perichondrium;two layers Inner chondrogenic layer outer fibrous layer

The growth of cartilage model; Intersititial growth Appositional growth Intersititial growth

Increase in the length

repeated division of chondrocytes production of additional matrix by the daughter cells.

Appositional growth

Widening of the model

addition of matrix to its periphery by new chondroblasts

As the differentiation of cells move towards metaphysis. Cells organize into longitudinal sections

Zone of proliferation

Zone of hypertrophy and maturation Zone of provisional and mineralization

 Zones

of proliferation;
The cells are small and flat Constitute a source of new cells

Zone of hypertrophy and maturation

The chondrocytes hypertrophy Secrete Type II collagen As hypertrophy proceeds, proteoglycans are secreted Partial breakdown of proteoglycans, creating a matrix environment receptive for mineral deposition

Zone of provisional mineralisation

Formation of matrix vesicles These membrane bound vesicles bud off from the cell and form independent units in the longitudinal septa of the cartilage

In this bone develops directly within the soft connective tissue rather than on a cartilaginous model

It involves following steps;

Formation of bone matrix within the fibrous membrane The mesenchymal cells proliferate and condense As vascularitry increases at the sites of condensed mesenchyme, osteoblasts differentiate and begin to produce bone matrix de nova

 At

the multiple sites within each bone of the cranial vault Maxilla Body of the mandible Midshaft of long bones

The bone spicules gradually lengthen into longer structures called as trabeculae The trabeculae extend in a radial pattern and these enclose blood vessels Woven bone;early membrane bone Periosteum ;external to woven bone, condensation of vascular mesenchyme.

 In

richly vascular areas, these osteogenic cells give rise to osteoblasts that form the bone matrix areas, with no capillary blood supply, they form the chondroblasts which lay down cartilage

In

Osteoblasts and osteogenic cells

Proliferate in a highly vascularised environment

osteoblasts

Deposit new layers of bone matrix on preexisting bone surface.

 Osteogenic

cells are always in superficial position repeating the process again and again

This

is appositional growth which result in build of bone tissue one layer at a time

The number of narrow canals are formed lined by osteogenic cells

These canals enclose blood vessels(in soft tissue spaces of cancellous network) The consecutive lamellae of bone become added to the bony walls of spaces in cancellous bone which is called osteon or haversian system

 Permit

skull and face to accommodate growing organs such as eyes and brain Same osteogenic potential as periosteum Skull bones forced apart by the growing brain-bone forms at the sutural margins, with waves of new bone cells differentiating from the cambium

Young immature bone is relatively thin, with few osteons. Its periosteal surface is undulating and forms bone rapidly Its endosteal surface is primarily for resorption.

The immature bone grows. Its periosteal surface is not as undulating and produce large number of secondary osteons. The primary osteons are resorbed.

The bone nearly matures.it is thicker still, its periosteal surface is less undulating and teritary osteons replace secondary osteons.Fragments of both primary and secondary osteons forms interstitial lamellae

 It

is the replacement of old bone by new bone

cone;

Cutting

The leading edge of resorption it is characterized in cross section by scalloped array of Howships lacunae,each housing an osteoclast

Remodeling is the major pathway of bony changes in shape, resistance to forces, repair of wounds, and calcium and phosphate homeostasis in the body.

Osteoclasts have resorbed organic matrix along with hydroxyapatite

The breakdown of collagen from the organic matrix releases various osteogenic substrates stimulates the differentiation of osteoblasts, which - deposit bone

Orbans: Oral Histology and Embryology 2000, 12th edition.

Ten Cates Oral Histology, Development, structure and function- 2005, 5th edition.