IDENTIFICATION OF MATRIX METALLOPROTEINASE-9 IN RABBIT OSTEOCLASTS

Osteoclasts are multinucleate giant cells that play key roles in bone resorption. To identify genes predominantly expressed in osteoclasts, we screened a cDNA library of osteoclasts with cDNA probes of osteocla sts and alveolar macrophages. Clones specifically hybridizing to the o steoclast probe were isolated and sequenced. The nucleotide sequence o f one such clone, F17, was found to share significant similarity with the sequences of human and mouse matrix metalloproteinase 9 (MMP-9) cD NA By isolation and sequencing of the full-length cDNA, F17 was reveal ed to encode the rabbit counterpart of MMP-9. By Northern blotting, me ssenger RNA for MMP-9 was found to be highly and predominantly express ed in isolated osteoclasts when compared with its level in alveolar ma crophages and other tissues. By gelatin zymography, gelatinase activit y was detected in conditioned medium of isolated osteoclasts, suggesti ng that MMP-9 is secreted by isolated osteoclasts. Expression of MMP-9 was also observed in in vivo osteoclasts in metacarpal bones of newbo rn rabbits by in situ hybridization. These facts suggest that MMP-9 is one of the major proteases produced by osteoclasts and possibly plays a role in osteoclastic bone resorption.