LOCALIZATION OF MESSENGER-RNA FOR COLLAGENASE IN OSTEOCYTIC, BONE SURFACE AND CHONDROCYTIC CELLS BUT NOT OSTEOCLASTS

Osteoclasts resorb the extracellular matrix of bone by secreting proto ns and enzymes into a circumpherentially sealed compartment between th e osteoclast and the bone surface. Although the lysosomal cysteine pro teinases play a major role in matrix degradation by osteoclasts, colla genase (matrix metalloproteinase-1, EC 3.4.24.7) is also required for osteoclastic bone resorption, and may be directly involved in collagen degradation in the hemivacuole. We assessed the effects of inhibitors of cysteine proteinases and collagenase on bone resorption by osteocl asts isolated from rodent bone. We found that while inhibition of cyst eine proteinases strongly suppressed osteoclastic resorption, inhibito rs of collagenase were without effect on the number, size, or deminera lised fringe of excavations. We could find no evidence of expression o f mRNA for collagenase in rat osteoclasts by in situ hybridisation, bu t found that it was expressed by chondrocytes, bone surface cells and osteocytes adjacent to osteoclasts. The distribution of these cells, a nd the correlation between increased collagenase production and increa sed stimulation of osteoclastic resorption in vitro by bone cells, sug gests that these cells might be involved in the regulation of bone res orption in situ, and that collagenase production might play a role in this process.