EXPRESSION OF 92-KD TYPE-IV COLLAGENASE (GELATINASE-B) IN THE OSTEOCLAST LINEAGE DURING MOUSE DEVELOPMENT

cDNA clones for murine 92 kD type IV collagenase (gelatinase B) were g enerated for the determination of its primary structure and for analys is of temporal and spatial expression in vivo. The mouse enzyme has 72 % sequence identity with the human counterpart, the major difference b eing the presence of a 16-residue segment absent from the human enzyme . In situ hybridization analyses of embryonic and postnatal mouse tiss ues revealed intense signals in cells of the osteoclast cell lineage. Clear expression above background was not observed in macrophages, pol ymorphonuclear leukocytes, monocytes, or epithelial cells which have b een shown to express the gene in vitro in cell cultures. Expression of the gene was first observed at early stage of cartilage and tooth dev elopment at E13, where signals were seen transiently in surrounding me senchymal cells. At later developmental stages and postnatally strong expression was seen in large cells at the surface of bones. These cell s were presumably osteoclasts as their location correlated with that o f TRAP positive cells. Signals above background were not observed in a number of other tissues studied. The results represent the first demo nstration of a highly osteoclast specific extracellular proteinase. Th e results suggest that during normal development of embryonic organs t he 92-kD type IV collagenase does not have a major role in basement me mbrane degradation, but is rather mainly used for the turnover of bone matrix, possibly as a gelatinase required for the removal of denature d collagen fragments (gelatin) generated by interstitial collagenase.