Bone - Structure & Function
Bone is is a specialised form of dense connective tissue.
Bone function =
Mechanical - gives the skeleton the necessary rigidity to function as attachment and lever for muscles and supports the body against gravity.
Chemical - Calcium homeostasis & metabolism
Three types of bone can be distinguished macroscopically:
Compact Bone (Cortical)
Trabecular Bone (Cancellous)
Lamellar bone forms both trabecular bone and compact bone, which are the two macroscopically recognizable bone forms.
Woven Bone (primary bone)
Bone from University
of Western Australia [click on picture for higher power view]
& Volkmann Canals from University
of Western Australia [click on picture for higher power view]
the formation and organization of the extracellular matrix of bone and its subsequent mineralisation.
synthesis of collagen & other bone proteins.
Derived from mesenchymal precursor cells / stem cells in marrow that have the potential to differentiate into fat cells, fibroblasts, chondrocytes or muscle cells (Owen & Ashton, 1986; Beresford, 1989).
Produce matrix, which comprises:
Type 1 collagen (90% of the protein in bone)
osteocalcin - see bone matrix below
They deposit osteoid on pre-existing mineralised surfaces only (= the mineralisation front).
A proportion of osteoblasts become trapped in lacunae within the matrix of bone as osteocytes, connected by a system of canaliculi.
Similar to nerve cells
Reside in lacunae
osteocytes have several thin processes, which extend from the lacunae into small channels within the bone, the canaliculi.
responsible for intercellular communication via canaliculi
regulate the response of bone to the mechanical environment (Skerry et al., 1989).
Resting surface cells (Bone Lining cells)
flat cell lying on the surface of bone
develops from osteoblasts, once they have completed their work
may dedifferentiate back into osteoblasts
large motile, multinucleated cell located on bone surfaces
Formed by the fusion of mononuclear cells derived from haematopoetic stem cells in marrow
[The theory that osteoclasts and osteoblasts are derived from different precursors has been challenged by a recent report proposing that stromal cells and haemopoetic cells have a common ancestry: a single multi-potential stem cell in marrow (Huang & Tertappen, 1992).]
have some features of macrophages
responsible for the resorption of bone matrix (osteoid)
Osteoclasts have a ruffled border of the cell membrane that is surrounded by an organelle-free region, or 'clear zone', and they adhere to the bone surface via integrins, which are specialised cell surface receptors (Vaes, 1988).
Functions: Osteoclastic bone resorption initially involves mineral dissolution, followed by degradation of the organic phase.
These processes take place beneath the ruffled border and depend on lysosomal enzyme secretion and an acid microenvironment (Baron, 1989).
A pH gradient across the ruffled membrane is the consequence of active transport mechanisms such as Na+/H+ exchange, ATP-dependent proton pumps, and the enzyme carbonic anhydrase (Baron et al., 1986; Blair et al., 1989; Sly et al., 1983).
Osteoclasts actively synthesise lysosomal enzymes, in particular the tartrate resistant isoenzyme of acid phosphatase (TRAP) (used as a marker of the osteoclast phenotype), and cysteine-proteinases such as the cathepsins that are capable of degrading collagen.
Lysosomal enzymes are only released at the ruffled border region of the osteoclast cell membrane (Baron, 1989).
Regulators of Osteoclast activity: [also see Metabolic Bone Disease]
Parathyroid hormone (PTH)
1,25 di-hydroxy vitamin D3[1,25(OH)2D3]
PTH and 1,25(OH)2D3 are unable to stimulate osteoclastic bone resorption in vitro in the absence of osteoblastic cells (McSheehy & Chambers, 1986). These agents stimulate osteoclasts to resorb bone via a 'coupling' factor.
Osteoclasts do not have receptors for 1,25(OH)2D3 (Merke et al., 1986), and until recently were not believed to have PTH receptors, although the functional significance of PTH receptors on osteoclasts remains to be established (Agarwal & Gay, 1992).
Osteoclasts have calcitonin receptors (Lin et al., 1991), and this inhibitor of bone resorption acts directly on the osteoclast to reduce cellular motility, retract cytoplasmic extensions and reduce ruffled border size.
IL-1, IL-6 & TNF - stimulate proliferation of osteoclast precursors
TGF beta - stimulates proliferation of osteoclast precursors in-vitro. Also has osteoblastic activation. (note - IGF & TGF are osteoblastic)
? Oestrogens - incr. expression of TGF beta; ? incr. nitric oxide from vascular endothelium; decr. IL6 (activates osteoclasts)
? Thyroid hormones
Biphosphonates - synthetic analogs of pyrophosphate, which act as an inhibitors of osteoclast-mediated bone resorption
Bone cells [OsCl = osteoclast; OC = osteocyte; OB = osteoblast; CC = calcified cartilage; B = bone]
ORGANIC COMPONENTS OF MATRIX
= 40% of the dry weight of bone
3. Matrix Proteins (non-collagenous)
INORGANIC COMPONENTS OF MATRIX
60% of dry weight of bone
1. Calcium Hydroxyapatite - Ca10(PO4)6(OH)2
2. Osteocalcium Phosphate (Brushite)
Remodelling = osteoclasts resorb bone & the resulting hole is filled by osteoblasts with new bone & osteocytes. (e.g. cutting cone of compact bone)
Modelling = osteoclasts remove bone from one area while osteoblasts add bone elsewhere. Occurs in trabecular bone in response to load changes (Wolff's Law).
Cortical / Compact bone:
The appendicular skeleton develop from the limb buds, which are mesodermal structures covered by ectoderm.
The first visible outline of the embryonic limb follows a condensation of mesenchymal cells which subsequently differentiate into cartilage cells, the chondrocytes.
These cells secrete a matrix and so produce cartilaginous models of the future bones. Surrounding this cartilage is the perichondrium, the outer layer of which becomes a connective tissue sheath while the inner cells remain pluripotential.
Primary, or diaphyseal ossification centre, develops at a site where the cartilage cells and matrix have begun to disintegrate. Trabecular bone is then deposited on cartilaginous remnants.
In long bones, another secondary centre of ossification appears at the growing cartilaginous ends, the epiphyseal ossification centre.
A transverse plate of cartilage extends across the bone separating the epiphyseal from the diaphyseal ossification centre = the physis / epiphyseal growth plate
Growth of cartilage in the epiphyseal plate is continuous, but the plate does not become thickened because on its diaphyseal side the cartilage matures, is calcified, resorbed and replaced by bone.
This is endochondral ossification, the mechanism responsible for increasing the length of the bone.
As an individual's height increases, the bone must increase its diameter, and this is achieved by new bone being laid down by the osteogenic layer of the periosteum.
This is intramembranous ossification that does not involve prior cartilage formation.
Bone, as an organ, receives 5-10% of cardiac output
Blood supply is from 4 sources:
Nutrient artery system
supplies the inner 2/3 of cortex from within (endosteal)
High pressure system
nutrient artery divides after reaching the medullary cavity, sending arteriole branches in proximal and distal directions to join with metaphyseal arteries
in the child, these vessels end on metaphyseal side of the physis & contribute to endochondral ossification.
forms an extensive network of vessels covers entire length of the bone shaft
supplies outer 1/3 of cortex
low pressure system
v. important in children, for circumferential bone growth (appositional)
supplies the zone of provisional calcification in the physis
anastomoses with the nutrient artery system
supplies following layers of physis by diffusion: resting, germinal, proliferating, and upper hypertrophic cell layers.
in femoral and radial heads which are almost entirely covered by cartilage the vessels enter in region between articular cartilage & growth-plate cartilage, and hence, the blood supply is tenuous.
Arterial supply of the cortex is centrifugal (inside to out). The direction is reversed in a displaced fracture, with disruption of the endosteal (nutrient) system.
Venous flow is centripetal with cortical capillaries draining to venous sinusoids to emissary venous system.
Connective tissue membrane covering bone
better developed in children because of it's role in the deposition of cortical bone (growth in bone diameter)
Inner Cambium Layer:
Outer Fibrous Layer:
contiguous with joint capsules
LF - Updated on: 23 December 2004 11:10