Bone contains three major cell types, Specialized Connective Tissue, Bone and Cartilage

Bone and Cartilage 

Bone contains three major cell types: osteoblasts that secrete type I collagen and noncollagenous proteins; osteocytes, which maintain mature bone; and osteoclasts, which resorb bone by acidification. Osteoclastic activity uses protons (H+) derived from carbonic acid formed by the enzyme carbonic anyhydrase. Carbonic anhydrases are zinc-containing enzymes that catalyse the reversible reaction between carbon dioxide hydration and bicarbonate dehydration:

H2O + CO2↔ H++ HCO3

In the region of the ruffled border, protons and lysosomal enzymes, such as acid phosphatase, are released into a sealed zone (Howship’s lacuna). Breakdown of bone occurs due to the acidification of this extracellular compartment that is analogous to an intracellular secondary lysosome.

Bone deposition 

Bone deposition is regulated primarily by parathyroid hormone (PTH), which is secreted in response to low serum calcium levels. PTH increases serum calcium as summarized below. The increased serum calcium inhibits PTH secretion by negative feedback. PTH stimulates: 

  • osteoclasts to resorb bone (through PTH receptors on osteoblasts),
  • renal synthesis of 1,25-dihydroxycholecalciferol, which in turn increases intestinal absorption of Ca++.
  • intestinal absorption of Ca++
PTH regulates osteoclasts by an indirect mechanism through PTH receptors on osteoblasts. There are no PTH receptors on osteoclasts. PTH stimulation of osteoblasts releases macrophage colony-stimulating factor (M-CSF) and RANK-L. M-CSF stimulates differentiation of monocytes into osteoclasts. RANK-L is found in both membrane and soluble forms and binds to RANK (receptor for activation of nuclear factor kappa B) on osteoclasts and osteoclast precursors stimulating osteoclastic activation/ruffled border formation. Osteoprotegerin (OPG) is a decoy receptor for RANK-L, binds RANK-L, and leads to inhibition of osteoclastic activity.
PTH regulates osteoclasts by an indirect mechanism through PTH receptors on osteoblasts. There are no PTH receptors on osteoclasts. PTH stimulation of osteoblasts releases macrophage colony-stimulating factor (M-CSF) and RANK-L. M-CSF stimulates differentiation of monocytes into osteoclasts. RANK-L is found in both membrane and soluble forms and binds to RANK (receptor for activation of nuclear factor kappa B) on osteoclasts and osteoclast precursors stimulating osteoclastic activation/ruffled border formation. Osteoprotegerin (OPG) is a decoy receptor for RANK-L, binds RANK-L, and leads to inhibition of osteoclastic activity.

Those molecules create the link between osteoblasts and osteoclasts known as the ARF (activation-resorption-formation) cycle in which activation of osteoclasts is inextricably linked to osteoblasts. This has been one of the problems in treating osteoporosis in which osteoclastic activity dominates osteoblastic activity. Growth factors such as transforming growth factorbeta (TGF-β) and insulin-like growth factors also play a role in differentiation of osteoblasts and osteoclasts. TGF-β is found in an inactive form in the bone matrix and is activated by acid produced by osteoclasts. TGF-β then inhibits osteoclast differentiation and stimulates osteoblastic activity.

GF = growth factors, OPG = osteoprotegerin, PR = parathyroid hormone receptor, PTH = parathyroid hormone, RANK = receptor for activation of nuclear factor kappa B, RANK-L = ligand for RANK, M-CSF = macrophage colony-stimulating factor, M-CSF-R = MCSF receptor.
GF = growth factors, OPG = osteoprotegerin, PR = parathyroid hormone receptor, PTH = parathyroid hormone, RANK = receptor for activation of nuclear factor kappa B, RANK-L = ligand for RANK, M-CSF = macrophage colony-stimulating factor, M-CSF-R = MCSF receptor.

Calcitonin opposes the actions of PTH, but plays a lesser role overall. Bone is highly vascular and mineralized with hydroxyapatite. In contrast, the three types of cartilage are avascular and contain chondrocytes that synthesize fibers and ground substance. Hyaline cartilage covers articular surfaces and forms the cartilage model in long bone development. Elastic cartilage is found in the pinna of the ear and in the epiglotlis, while fibrocartilage is an intermediate form found in the intervertebral disc, pubic symphysis, and connecting tendon and bone. Hyaline cartilage contains matrix comprised of type II collagen electrostatically bound to proteoglycans. Elastic cartilage contains type II collagen and elastic fibers, and fibrocartilage, like bone, contains type I collagen.

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