The role of collagenase in bone resorption. An overview

Abstract

Since its discovery, vertebrate collagenase is postulated to be the key enzyme for collagen degradation, but the evidence for its participation in bone resorption was, until recently, very weak. The osteoclast, which is the major bone resorbing cell, does apparently not produce collagenase but lysosomal acid proteinases, including collagenolytic cysteine proteinases, whose involvement in bone resorption is supported by many observations. Recent reports indicating 1) that osteoblasts produce and secrete collagenase in response to bone resorbing hormones and 2) that bone resorption is inhibited by a specific collagenase inhibitor, have reintroduced collagenase as a plausible participant in the mechanisms of bone resorption. Moreover bone resorbing agents do not act directly on osteoclasts, but on osteoblasts which, by an unknown mechanism, induce the osteoclasts to excavate bone matrix. Collagenase could participate in the control of bone resorption by degrading the unmineralized collagen which seems to shield the underlying bone from osteoclastic attack. In addition, collagenase, stored as a latent proenzyme in the mineralized matrix, might cooperate with the lysosomal cysteine proteinases in the subosteoclastic lysis of demineralized collagen.