MOLECULAR-CLONING OF HUMAN CDNA FOR CATHEPSIN-K - NOVEL CYSTEINE PROTEINASE PREDOMINANTLY EXPRESSED IN BONE

We have previously cloned a rabbit cDNA clone (OC-2) from an osteoclas t cDNA library by the differential screening. OC-2 was found to encode a novel cysteine proteinase, tentatively called cathepsin K, which is predominantly expressed in osteoclasts. By use of a rabbit OC-2 fragm ent as a probe, its human counterpart was cloned from a cDNA library o f osteoarthritic hip bone. The cloned human cDNA (hOC-2) encoded a pro tein of 329 amino acid residues and its deduced amino acid sequence sh owed 94% homology to rabbit cathepsin K. Multiple alignment of amino a cid sequences of human cathepsins B, H, L, S and K showed the highest homology of cathepsin K to cathepsin S 48%. Northern blot analysis sho wed that cathepsin K mRNA is expressed at high levels in some osteoart hritic hip bones and at a very high level in osteoclastoma compared to very low levels in other tissues. These results suggest that cathepsi n K is closely involved in human osteoclastic bone resorption. (C) 199 5 Academic Press, Inc.