The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics.
Human cysteine proteases of the papain family have been recognized as potential drug targets for musculoskeletal diseases. Most of the interest is focused on cathepsins S and K, which display selective expression in cells of the immune system and cells capable to efficiently degrade extracellular matrix proteins, in particular collagens. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel anti-resorptive drugs in osteoporosis whereas cathepsin S appears to be an attractive drug target candidate for various inflammatory diseases including rheumatoid arthritis. Since rheumatoid arthritis is at the same time an inflammatory and joint destructive disorder, the combined inhibition of both cathepsins S and K should be beneficial. This review will outline the rationale and recent progress for targeting cathepsins in arthritis and osteoporosis.
Yasuda
Yoshiyuki
Y
University of British Columbia, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, 2199 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
Kaleta
Jadwiga
J
Brömme
Dieter
D
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002986:Clinical Trials as Topic; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K