Collagen lysosomal enzymes

Osteoclasts are multinucleated cells found on the endosteal surface of bone, in Haversian systems and periosteal surfaces. PTH activates osteoclasts (indirectly via osteoblasts that possess PTH receptors). Calcitonin is a potent inhibitor of osteoclast activity. Local cytokine factors, including interleukin-1 (IL-1), tumour-necrosis factor (TNF), TGF- 0 and interferon-y (INF-y), are important regulators. Osteoclast resorption of bone releases collagen peptides, pyridinoline cross-links and calcium from the bone matrix, through the action of lysosomal enzymes (collagenases and cathepsins). The collagen breakdown products in serum and urine (e.g. hydroxyproline) can be used as biochemical markers. 

Bone specific acid phosphatase A lysosomal enzyme of osteoclasts Urine Markers All of these are collagen breakdown products... 

Denatured collagen, as formed post-mortem by the action of lactic acid, can also be cleaved by lysosomal enzymes, e. g., lysosomal collagenase and cysteine proteinase cathepsin Bi. Thermally denatured collagen is attacked by pepsin and trypsin. 

Hydrochloric acid in the demineralizing compartment dissolves the bone mineral and denatures exposed collagen fibers for hydrolysis by cathepsin K. This lysosomal endopro-tease (Fig. 10.4a and b) has a cysteine thiol group at its catalytic center (Table 7.1 Fig. 10.4c). Cathepsin K is secreted in larger amounts than other lysosomal proteases and its specificity is due to unique amino acid residues around the peptide binding site. The enzyme hydrolyzes a) ) and a2(I) polypeptides from incompletely denatured fibers in the demineralizing compartment, leaving the cross-linked, telopeptide ends (Sect. 4.2.2). 

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