抄録
Osteoclasts are multinucleate giant cells playing key roles in bone resorption. These cells solubilize mineralized bone matrix by means of acid and protease action ; however, the precise mechanism of this process is not well known. Recently, we succeeded in the isolation of pure osteoclasts from rabbit bones and constructed a cDNA library. Using a differential screening procedure, two genes expressed predominantly in osteoclasts compared with spleen cells were isolated. One of them, OC-2, was found to encode a possible cysteine proteinase structurally related to cathepsins L and S.
Moreover, by use of a rabbit OC-2 fragment as a probe, its human counterpart was cloned from a cDNA library of osteoarthritic hip bone. The cloned human cDNA (hOC-2) encoded a protein of 329 amino acid residues and its deduced amino acid sequence showed 94% homology to rabbit cathepsin K. Multiple alignment of amino acid sequences of human cathepsins B, H, L, S and K showed the highest homology of cathepsin K to cathepsin S 48%. Northern blot analysis showed that cathepsin K mRNA is expressed at high levels in some osteoarthritic hip bone and at a very high level in osteoclastoma compared to very low levels in other tissues. These results suggest that cathepsin K is closely involved in human osteoclastic bone resorption.
