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The protein encoded by this gene is a lysosomal cysteine protease involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is expressed predominantly in osteoclasts.
Cathepsin K is a protease, which is defined by its high specificity for kinins, that is involved in bone resorption. The enzyme's ability to catabolize elastin, collagen, and gelatin allows it to break down bone and cartilage. This catabolic activity is also partially responsible for the loss of lung elasticity and recoil in emphysema. Cathepsin K inhibitors show great potential in the treatment of osteoporosis. Cathepsin K is degraded by Cathepsin S, called Controlled Cathepsin Cannibalism.
Cathepsin K is expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness.[3] Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature.[4] Cathepsin K has also been found to be over-expressed in glioblastoma.[5]
That the expression of cathepsin K is characteristic for some cancers and not others has been documented.[6] Cathepsin K antibodies are marketed for research into expression of this enyzme by various cells.[7][8][9]
Merck had a cathepsin K inhibitor, odanacatib, in Phase III clinical trials for osteoporosis. In September, 2016, Merck announced they were discontinuing development of odanacatib after their own assessment of adverse events and an independent assessment showed increased risk of stroke.[10][11] Other cathepsin K inhibitors are in various stages of development.[12][13][14]Medivir has a cathepsin K inhibitor, MIV-711 (L-006235[15][16][17]), in Phase IIa clinical trial, as a disease modifying osteoarthritis drug, as of October 2017.
↑""CTSK cathepsin K [ Homo sapiens (human) ]"". NCBI Gene. National Center for Biotechnology Information, U.S. National Library of Medicine. 4 September 2016. Retrieved 2 October 2016.
↑Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H,. (2008). Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science, 319(5863), 624-627.
↑Hussein, H., Ishihara, A., Menendez, M., & Bertone, A. (2014). Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses. Journal of veterinary pharmacology and therapeutics.
Motyckova G, Fisher DE (2003). "Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease". Curr. Mol. Med. 2 (5): 407–21. doi:10.2174/1566524023362401. PMID12125807.
Shi GP, Chapman HA, Bhairi SM, et al. (1995). "Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2". FEBS Lett. 357 (2): 129–34. doi:10.1016/0014-5793(94)01349-6. PMID7805878.
Inaoka T, Bilbe G, Ishibashi O, et al. (1995). "Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone". Biochem. Biophys. Res. Commun. 206 (1): 89–96. doi:10.1006/bbrc.1995.1013. PMID7818555.
Velasco G, Ferrando AA, Puente XS, et al. (1994). "Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues". J. Biol. Chem. 269 (43): 27136–42. PMID7929457.
Li YP, Alexander M, Wucherpfennig AL, et al. (1996). "Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas". J. Bone Miner. Res. 10 (8): 1197–202. doi:10.1002/jbmr.5650100809. PMID8585423.
Bossard MJ, Tomaszek TA, Thompson SK, et al. (1996). "Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification". J. Biol. Chem. 271 (21): 12517–24. doi:10.1074/jbc.271.21.12517. PMID8647860.
Gelb BD, Shi GP, Chapman HA, Desnick RJ (1996). "Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency". Science. 273 (5279): 1236–8. doi:10.1126/science.273.5279.1236. PMID8703060.
Johnson MR, Polymeropoulos MH, Vos HL, et al. (1997). "A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis". Genome Res. 6 (11): 1050–5. doi:10.1101/gr.6.11.1050. PMID8938428.
Littlewood-Evans A, Kokubo T, Ishibashi O, et al. (1997). "Localization of cathepsin K in human osteoclasts by in situ hybridization and immunohistochemistry". Bone. 20 (2): 81–6. doi:10.1016/S8756-3282(96)00351-1. PMID9028530.
McGrath ME, Klaus JL, Barnes MG, Brömme D (1997). "Crystal structure of human cathepsin K complexed with a potent inhibitor". Nat. Struct. Biol. 4 (2): 105–9. doi:10.1038/nsb0297-105. PMID9033587.
Rood JA, Van Horn S, Drake FH, et al. (1997). "Genomic organization and chromosome localization of the human cathepsin K gene (CTSK)". Genomics. 41 (2): 169–76. doi:10.1006/geno.1997.4614. PMID9143491.
Gelb BD, Shi GP, Heller M, et al. (1997). "Structure and chromosomal assignment of the human cathepsin K gene". Genomics. 41 (2): 258–62. doi:10.1006/geno.1997.4631. PMID9143502.
Gomes RA, Juliano L, Chagas JR, Hial V (1997). "Characterization of kininogenase activity of an acidic proteinase isolated from human kidney". Can. J. Physiol. Pharmacol. 75 (6): 757–61. doi:10.1139/cjpp-75-6-757. PMID9276160.
