title: Cathepsins in the osteoclast.
abstract: The mechanism by which bone collagen and other organic components are degraded by the osteoclast during osteoclastic bone resorption was unclear until the 1980s. Studies conducted since the early 1990s have identified lysosomal proteases, mainly cathepsins that are active at low pH, involved in osteoclastic bone resorption. Several cathepsins, such as cathepsins C, D, B, E, G and L, were initially demonstrated to take part in the degradation of organic bone matrix in osteoclasts. Cathepsin K, which has high proteolytic activity and localizes primarily in osteoclasts, was discovered in 1995. This first tissue-specific cathepsin was associated with pycnodysostosis, a genetic disorder observable as an osteopetrotic phenotype in cathepsin K-deficient mice. Cystatin C, an endogenous inhibitor of cysteine proteases, regulates the activity of cathepsin K. However, detailed morphological observations suggest that the organic bone matrix is degraded by not only cathepsin K, but also by matrix metalloproteinases or other cathepsins. The osteoclast possesses a unique endocytotic/exocytotic structure and each cathepsin is specifically localized in the osteoclast, which implies that each cathepsin contributes cooperatively to the process of osteoclastic bone resorption. Further studies may clarify the regulation of cathepsin activities and the roles of cathepsins during bone remodelling.
authors.affiliation: Department of Oral Anatomy, Kyushu Dental College, 2-9-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan. tgoto@kyu-dent.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Goto
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yamaza
authors.forename: Teruo
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D001862:Bone Resorption; D002403:Cathepsins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000201:enzymology* / Q000502:physiology; D011817:Rabbits; D051381:Rats
chemical_list: D002403:Cathepsins