MOLECULAR-CLONING OF A POSSIBLE CYSTEINE PROTEINASE PREDOMINANTLY EXPRESSED IN OSTEOCLASTS

Osteoclasts are multinucleate giant cells playing key roles in bone re sorption. These cells solubilize mineralized bone matrix by means of a cid and protease action; however, the precise mechanism of this proces s is not well known. Recently, we succeeded in the isolation of pure o steoclasts from rabbit bones and constructed a cDNA library. Using a d ifferential screening procedure, two genes expressed predominantly in osteoclasts compared with spleen cells were isolated (Tezuka, K., Sato , T., Kamioka, H., Nijweide, P. J., Tanaka, K., Matsuo, T., Ohta, M., Kurihara, N., Hakeda, Y., and Kumegawa, M. (1992) Biochem. Biophys. Re s. Commun. 186, 911-917). One of them, OC-2, was found to encode a pos sible cysteine proteinase structurally related to cathepsins L and S. By in situ hybridization, OC-2 was confirmed to be expressed in osteoc lasts in vivo. By Northern blot analysis, OC-2 was highly and preferen tially expressed in osteoclasts compared with other tissues such as ki dney, liver, spleen, and lung. The predominant expression of OC-2 in o steoclasts may suggest that OC-2 encodes a protein, possibly a cystein e proteinase, that plays an important role in osteoclastic bone resorp tion.