IBMS BoneKEy | Perspective

Cathepsin K – A new molecular target for osteoporosis

Sevgi B Rodan
Le T Duong

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DOI:10.1138/20080294

Abstract

Cathepsin K (Cat K) is a cysteine protease of the papain family, now considered to be the major enzyme responsible for degradation of the organic bone matrix. It is highly and selectively expressed in osteoclasts and, under acidic conditions, has the unique ability to degrade type I collagen helical regions. Complete deficiency of Cat K activity leads to pycnodysostosis, a severe and rare autosomal recessive bone sclerotic disorder, and Cat K null-mice are osteopetrotic. Thus this protease is an attractive target for inhibition of bone resorption. Cat K inhibitors have been reviewed recently. Therefore, the following Perspective will focus on inhibitors that have been extensively characterized in animal models of bone loss, particularly the inhibitors that have advanced to clinical trials for the treatment of osteoporosis. Other disease targets such as osteoarthritis and bone metastasis will also be discussed.

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