Abstract
Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.
Highlights
Lysosomal cysteine proteases, firstly discovered in the 20s of the twentieth century, are generally called cathepsins nowadays
The Cathepsin K (CatK)-deficient mice revealed the milder cartilage degradation after anterior cruciate ligament transection (ACLT) when compared with wildtype controls (Hayami et al, 2012), whereas the CatK transgenic mice spontaneously developed synovitis and cartilage degradation (Morko et al, 2005). These findings suggest that the increased expression and collagenase activity of CatK could contribute to the cartilage matrix degradation in OA progression
Administration of NC-2300, an inhibitor of most of cysteine proteases, could prevent cerebral aneurysm (CA) progression in rats by inhibiting extracellular matrix (ECM) degradation in aneurysmal walls caused by cysteine cathepsins. These results suggest that inhibition of CatK might be beneficial for preventing CA progression
Summary
Firstly discovered in the 20s of the twentieth century, are generally called cathepsins nowadays. Cathepsin K (CatK) is predominantly secreted by activated osteoclasts to degrade collagen and other matrix proteins during bone resorption (Costa et al, 2011).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
