Answer to Question #101658 in Cell Biology for Laila

Question

Histological structure and regeneration of bone and cartilage. Write about the cells involved, along with their roles and how they are activated.

Answer 1

Chondroblasts appear to migrate to cartilage whenever chondrocytes are destroyed via mechanical force. Remaining chondrocytes divide in order to form more chondroblasts. HMGB-1, a growth factor which promotes chondrocyte division while receptors for advanced glycation products (RAGE) mediated chemotaxis to clean up cell debris resulting from the damage. Chondroblasts then secrete cartilage matrix around themselves in order to reform the lost cartilage tissue.

Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Chondrocytes express the VDR and 1,25(OH)2D3 has a biphasic effect on chondrocyte proliferation, being stimulatory at physiological concentrations (10−12 M) and inhibitory at high concentrations (10−8 M). Characteristics of chondrocyte differentiation, such as alkaline phosphatase expression, collagen production, and matrix calcification, are affected by 1,25(OH)2D3 treatment in vitro. The expression of and signaling by several factors modulating chondrocyte development, such as IGF-I and IGF-I receptor, is influenced by 1,25(OH)2D3. 1,25(OH)2D3 has also been reported to increase apoptosis in mouse hypertrophic chondrocytes.

Osteoblasts are cells with a single nucleus that synthesize bone. They synthesize dense, crosslinked collagen and specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which compose the organic matrix of bone. In organized groups of connected cells, osteoblasts produce hydroxylapatite - the bone mineral, that is deposited in a highly regulated manner, into the organic matrix forming a strong and dense mineralized tissue - the mineralized matrix. The mineralized skeleton is the main support for the bodies of air breathing vertebrates. It is an important store of minerals for physiological homeostasis including both acid-base balance and calcium or phosphate maintenance.

An osteoclast is a type of bone cell that breaks down bone tissue. Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in small cavities called Howship's lacunae, formed from the digestion of the underlying bone. The sealing zone is the attachment of the osteoclast's plasma membrane to the underlying bone. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin. The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled border into the resorptive cavity, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped against a high concentration gradient by proton pumps, specifically a unique vacuolar-ATPase. This enzyme has been targeted in the prevention of osteoporosis. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease (MMP) groups, are released to digest the organic components of the matrix. These enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance.

Osteocytes synthesize sclerostin, a secreted protein that inhibits bone formation by binding to LRP5/LRP6 coreceptors and blunting Wnt signaling. Sclerostin, the product of the SOST gene, is the first mediator of communication between osteocytes, bone forming osteoblasts and bone resorbing osteoclasts, critical for bone remodeling.Only osteocytes express sclerostin, which acts in a paracrine fashion to inhibit bone formation. Sclerostin is inhibited by parathyroid hormone (PTH) and mechanical loading. Sclerostin antagonizes the activity of BMP (bone morphogenetic protein), a cytokine that induces bone and cartilage formation