cathepsin K

Summary

Gene Symbol: cathepsin K
Description: cathepsin K
Alias: AI323530, MMS10-Q, Ms10q, catK, cathepsin K, Cat K
Species: mouse
Products:     cathepsin K

Top Publications

  1. Asagiri M, Hirai T, Kunigami T, Kamano S, Gober H, Okamoto K, et al. Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science. 2008;319:624-7 pubmed publisher
    b>Cathepsin K was originally identified as an osteoclast-specific lysosomal protease, the inhibitor of which has been considered might have therapeutic potential...
  2. Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A. 1998;95:13453-8 pubmed
    b>Cathepsin K is a recently identified lysosomal cysteine proteinase. It is abundant in osteoclasts, where it is believed to play a vital role in the resorption and remodeling of bone...
  3. Lutgens S, Kisters N, Lutgens E, van Haaften R, Evelo C, de Winther M, et al. Gene profiling of cathepsin K deficiency in atherogenesis: profibrotic but lipogenic. J Pathol. 2006;210:334-43 pubmed
    Recently, we showed that cathepsin K deficiency reduces atherosclerotic plaque progression, induces plaque fibrosis, but aggravates macrophage foam cell formation in the ApoE -/- mouse...
  4. Samokhin A, Wilson S, Nho B, Lizame M, Musenden O, Bromme D. Cholate-containing high-fat diet induces the formation of multinucleated giant cells in atherosclerotic plaques of apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol. 2010;30:1166-73 pubmed publisher
    ..Most of the MGCs stained intensively for cathepsin K and were located at fibrous caps and close to damaged elastic laminae, with associated medial smooth muscle ..
  5. Buhling F, Rocken C, Brasch F, Hartig R, Yasuda Y, Saftig P, et al. Pivotal role of cathepsin K in lung fibrosis. Am J Pathol. 2004;164:2203-16 pubmed
    ..This study examined the putative role of cathepsin K (catK) in the pathology of lung fibrosis in mice and its relevance to the human disease activity...
  6. van den Brule S, Misson P, Buhling F, Lison D, Huaux F. Overexpression of cathepsin K during silica-induced lung fibrosis and control by TGF-beta. Respir Res. 2005;6:84 pubmed
    ..5 mg crystalline silica or other particles. Cat expression (Cat K, S, L and B) was quantified in lung tissue and isolated pulmonary cells by quantitative RT-PCR...
  7. Samokhin A, Wong A, Saftig P, Bromme D. Role of cathepsin K in structural changes in brachiocephalic artery during progression of atherosclerosis in apoE-deficient mice. Atherosclerosis. 2008;200:58-68 pubmed publisher
    b>Cathepsin K, a potent extracellular matrix degrading cysteine protease, has been linked to the pathogenesis of osteoporosis, arthritis, cardiovascular and respiratory diseases...
  8. Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell. 2007;130:811-23 pubmed
    ..Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs. ..
  9. Li C, Jepsen K, Majeska R, Zhang J, Ni R, Gelb B, et al. Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass. J Bone Miner Res. 2006;21:865-75 pubmed
    Bone microstructural and biomechanical properties were analyzed in mice genetically lacking cathepsin K (CatK)...

More Information

Publications87

  1. Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, et al. The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice. J Clin Invest. 2009;119:3149-59 pubmed publisher
    ..by mating Bcl-xfl/fl mice with mice in which the gene encoding the Cre recombinase has been knocked into the cathepsin K locus and specifically expressed in mature osteoclasts...
  2. Zhang D, Leung N, Weber E, Saftig P, Bromme D. The effect of cathepsin K deficiency on airway development and TGF-?1 degradation. Respir Res. 2011;12:72 pubmed publisher
    b>Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is a major drug target for the treatment of osteoporosis. Recent findings, however, indicate that cathepsin K is also involved in non-skeletal metabolism...
  3. Friedrichs B, Tepel C, Reinheckel T, Deussing J, von Figura K, Herzog V, et al. Thyroid functions of mouse cathepsins B, K, and L. J Clin Invest. 2003;111:1733-45 pubmed
    ..Cathepsin L was upregulated in thyroids of cathepsin K(-/-) or B(-/-)/K(-/-) mice, suggesting a compensation of cathepsin L for cathepsin K deficiency...
  4. Rantakokko J, Aro H, Savontaus M, Vuorio E. Mouse cathepsin K: cDNA cloning and predominant expression of the gene in osteoclasts, and in some hypertrophying chondrocytes during mouse development. FEBS Lett. 1996;393:307-13 pubmed
    ..The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences...
  5. Dodds R, Connor J, Drake F, Feild J, Gowen M. Cathepsin K mRNA detection is restricted to osteoclasts during fetal mouse development. J Bone Miner Res. 1998;13:673-82 pubmed
    We recently identified a novel cysteine protease, cathepsin K, by random sequencing of an osteoclast cDNA library, and in situ hybridization studies in adult human tissues demonstrated high and specific expression in osteoclasts...
  6. Zhu C, Morse L, Battaglino R. SNX10 is required for osteoclast formation and resorption activity. J Cell Biochem. 2012;113:1608-15 pubmed publisher
  7. Lutgens E, Lutgens S, Faber B, Heeneman S, Gijbels M, de Winther M, et al. Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation. 2006;113:98-107 pubmed
    b>Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly ..
  8. Hua Y, Zhang Y, Dolence J, Shi G, Ren J, Nair S. Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunction. Diabetes. 2013;62:498-509 pubmed publisher
    The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease. We hypothesized that ablation of cathepsin K protects against obesity-associated cardiac dysfunction...
  9. Tepel C, Bromme D, Herzog V, Brix K. Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J Cell Sci. 2000;113 Pt 24:4487-98 pubmed
    ..Here, we report on the expression of the cysteine protease cathepsin K in thyroid epithelial cells...
  10. Gelb B, Shi G, Chapman H, Desnick R. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996;273:1236-8 pubmed
    ..b>Cathepsin K, a cysteine protease gene that is highly expressed in osteoclasts, localized to the pycnodysostosis region...
  11. Funicello M, Novelli M, Ragni M, Vottari T, Cocuzza C, Soriano Lopez J, et al. Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores. PLoS ONE. 2007;2:e683 pubmed
    ..We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white adipose tissue (WAT) of obese individuals...
  12. Hua Y, Xu X, Shi G, Chicco A, Ren J, Nair S. Cathepsin K knockout alleviates pressure overload-induced cardiac hypertrophy. Hypertension. 2013;61:1184-92 pubmed publisher
    Evidence from human and animal studies has documented elevated levels of lysosomal cysteine protease cathepsin K in failing hearts...
  13. Kiviranta R, Morko J, Alatalo S, NicAmhlaoibh R, Risteli J, Laitala Leinonen T, et al. Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone. 2005;36:159-72 pubmed
    Previous reports indicate that mice deficient for cathepsin K (Ctsk), a key protease in osteoclastic bone resorption, develop osteopetrosis due to their inability to properly degrade organic bone matrix...
  14. Yang M, Sun J, Zhang T, Liu J, Zhang J, Shi M, et al. Deficiency and inhibition of cathepsin K reduce body weight gain and increase glucose metabolism in mice. Arterioscler Thromb Vasc Biol. 2008;28:2202-8 pubmed publisher
    ..We now provide evidence from a mouse model of obesity to suggest a direct participation of cathepsin K (CatK) in mouse body weight gain and glucose metabolism...
  15. Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, LaCombe J, et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013;123:2421-33 pubmed
    ..This study uncovers the existence of a second endocrine axis that is necessary for optimal male fertility in the mouse and suggests that osteocalcin modulates reproductive function in humans...
  16. Gentile M, Soung D, Horrell C, Samadfam R, Drissi H, Duong L. Increased fracture callus mineralization and strength in cathepsin K knockout mice. Bone. 2014;66:72-81 pubmed publisher
    b>Cathepsin K (CatK) is a cysteine protease, expressed predominantly in osteoclasts (OC) which degrades demineralized bone matrix...
  17. Greenblatt M, Park K, Oh H, Kim J, Shin D, Lee J, et al. CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts. J Exp Med. 2015;212:1283-301 pubmed publisher
    ..Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder. ..
  18. Shin N, Choi H, Neff L, Wu Y, Saito H, Ferguson S, et al. Dynamin and endocytosis are required for the fusion of osteoclasts and myoblasts. J Cell Biol. 2014;207:73-89 pubmed publisher
  19. Leung P, Pickarski M, Zhuo Y, Masarachia P, Duong L. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone. 2011;49:623-35 pubmed publisher
    Odanacatib (ODN) is a selective, potent and reversible inhibitor of cathepsin K (CatK) that inhibits bone loss in postmenopausal osteoporosis...
  20. Jensen J, Peters L, Borrego A, Ribeiro O, Cabrera W, Starobinas N, et al. Involvement of antibody production quantitative trait loci in the susceptibility to pristane-induced arthritis in the mouse. Genes Immun. 2006;7:44-50 pubmed
    ..Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes. ..
  21. Hao L, Zhu G, Lu Y, Wang M, Jules J, Zhou X, et al. Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role. FEBS Lett. 2015;589:1331-1339 pubmed publisher
    ..We reveal that genetic deletion of cathepsin K (Ctsk) caused a radical reduction in inflammation and bone erosion within RA joint capsules and periodontal ..
  22. Dai Q, Xie F, Han Y, Ma X, Zhou S, Jiang L, et al. Inactivation of Regulatory-associated Protein of mTOR (Raptor)/Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling in Osteoclasts Increases Bone Mass by Inhibiting Osteoclast Differentiation in Mice. J Biol Chem. 2017;292:196-204 pubmed publisher
  23. Okaji M, Sakai H, Sakai E, Shibata M, Hashimoto F, Kobayashi Y, et al. The regulation of bone resorption in tooth formation and eruption processes in mouse alveolar crest devoid of cathepsin k. J Pharmacol Sci. 2003;91:285-94 pubmed
    Osteoclastic bone resorption has recently been implicated in the tooth formation and eruption in alveolar bone. Cathepsin K (CK) is a cysteine proteinase expressed predominantly in osteoclasts and is believed to play a critical role in ..
  24. Zhu B, Suzuki K, Goldberg H, Rittling S, Denhardt D, McCulloch C, et al. Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors: evidence of a role for an intracellular form of osteopontin. J Cell Physiol. 2004;198:155-67 pubmed
  25. Johnson R, McGregor N, Brennan H, Crimeen Irwin B, Poulton I, Martin T, et al. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone. Bone. 2015;81:343-51 pubmed publisher
    ..To determine the critical roles of gp130 signalling in the osteoclast, we generated mice using cathepsin K Cre (CtskCre) to disrupt gp130 signalling in osteoclasts. Bone marrow macrophages from CtskCre...
  26. Zenger S, Ek Rylander B, Andersson G. Long bone osteoclasts display an augmented osteoclast phenotype compared to calvarial osteoclasts. Biochem Biophys Res Commun. 2010;394:743-9 pubmed publisher
    ..bone and characterized by high expression of the enzymes tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK)...
  27. LaCombe J, Karsenty G, Ferron M. In vivo analysis of the contribution of bone resorption to the control of glucose metabolism in mice. Mol Metab. 2013;2:498-504 pubmed publisher
    ..These results support the notion that osteoclasts are controlling glucose metabolism at least in part through the regulation of osteocalcin decarboxylation. ..
  28. Rantakokko J, Kiviranta R, Eerola R, Aro H, Vuorio E. Complete genomic structure of the mouse cathepsin K gene (Ctsk) and its localization next to the Arnt gene on mouse chromosome 3. Matrix Biol. 1999;18:155-61 pubmed
    ..for gene manipulative experiments in mice we have isolated genomic clones covering the entire murine cathepsin K gene (Ctsk). Sequence analysis revealed that the gene spans 10.1 kb and contains eight exons and seven introns...
  29. Platt M, Ankeny R, Shi G, Weiss D, Vega J, Taylor W, et al. Expression of cathepsin K is regulated by shear stress in cultured endothelial cells and is increased in endothelium in human atherosclerosis. Am J Physiol Heart Circ Physiol. 2007;292:H1479-86 pubmed
    ..occurs in arteries exposed to disturbed flow conditions, we hypothesized that shear stress would regulate cathepsin K expression and activity in endothelial cells...
  30. Han J, Luo T, Gu Y, Li G, Jia W, Luo M. Cathepsin K regulates adipocyte differentiation: possible involvement of type I collagen degradation. Endocr J. 2009;56:55-63 pubmed
    We previously found that cathepsin K (CTSK) played an important role in adipocyte differentiation. However, the underlying molecular mechanism is not clear...
  31. Sausbier U, Dullin C, Missbach Guentner J, Kabagema C, Flockerzie K, Kuscher G, et al. Osteopenia due to enhanced cathepsin K release by BK channel ablation in osteoclasts. PLoS ONE. 2011;6:e21168 pubmed publisher
    The process of bone resorption by osteoclasts is regulated by Cathepsin K, the lysosomal collagenase responsible for the degradation of the organic bone matrix during bone remodeling...
  32. Fukunaga T, Zou W, Warren J, Teitelbaum S. Vinculin regulates osteoclast function. J Biol Chem. 2014;289:13554-64 pubmed publisher
    ..Thus, we mated VCL(fl/fl) mice with those expressing cathepsin K-Cre (CtsK-VCL) to delete the gene in mature osteoclasts or lysozyme M-Cre (LysM-VCL) to target all osteoclast ..
  33. Guo Y, Wang L, Ma R, Mu Q, Yu N, Zhang Y, et al. JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice. Life Sci. 2016;148:24-30 pubmed publisher
    ..The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining...
  34. Guo J, Bot I, de Nooijer R, Hoffman S, Stroup G, Biessen E, et al. Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice. Cardiovasc Res. 2009;81:278-85 pubmed publisher
    b>Cathepsin K (CatK), an established drug target for osteoporosis, has been reported to be upregulated in atherosclerotic lesions. Due to its proteolytic activity, CatK may influence the atherosclerotic lesion composition and stability...
  35. Haraguchi R, Kitazawa R, Mori K, Tachibana R, Kiyonari H, Imai Y, et al. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss. Sci Rep. 2016;6:25198 pubmed publisher
  36. Wiig H, Schröder A, Neuhofer W, Jantsch J, Kopp C, Karlsen T, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123:2803-15 pubmed publisher
  37. Zhou Y, Mohan A, Moore D, Lin L, Zhou F, Cao J, et al. SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion. FASEB J. 2015;29:1635-45 pubmed publisher
    ..Shp2 or its signaling partners could potentially serve as pharmacological targets to regulate the population of OCs locally and/or systematically, and thus treat OC-related diseases, such as periprosthetic osteolysis and osteoporosis. ..
  38. Hua Y, Robinson T, Cao Y, Shi G, Ren J, Nair S. Cathepsin K knockout alleviates aging-induced cardiac dysfunction. Aging Cell. 2015;14:345-51 pubmed publisher
    Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects ..
  39. Miyazaki T, Iwasawa M, Nakashima T, Mori S, Shigemoto K, Nakamura H, et al. Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption. J Biol Chem. 2012;287:37808-23 pubmed publisher
  40. Donners M, Bai L, Lutgens S, Wijnands E, Johnson J, Schurgers L, et al. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice. PLoS ONE. 2016;11:e0162595 pubmed publisher
    b>Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses...
  41. Yu T, Kondo T, Matsumoto T, Fujii Kuriyama Y, Imai Y. Aryl hydrocarbon receptor catabolic activity in bone metabolism is osteoclast dependent in vivo. Biochem Biophys Res Commun. 2014;450:416-22 pubmed publisher
  42. Arampatzidou M, Schütte A, Hansson G, Saftig P, Brix K. Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon. Biol Chem. 2012;393:1391-403 pubmed publisher
    b>Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory activities in the mouse colon...
  43. Wu M, Chen W, Lu Y, Zhu G, Hao L, Li Y. Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway. Nat Commun. 2017;8:13700 pubmed publisher
  44. Shinohara M, Nakamura M, Masuda H, Hirose J, Kadono Y, Iwasawa M, et al. Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B-mediated vesicle transport. J Bone Miner Res. 2012;27:2464-75 pubmed publisher
    ..Thus, the class IA PI3K-Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases...
  45. Winkeler C, Kladney R, Maggi L, Weber J. Cathepsin K-Cre causes unexpected germline deletion of genes in mice. PLoS ONE. 2012;7:e42005 pubmed publisher
    ..The primary protease responsible for the degradation of the organic component of the bone matrix is Cathepsin K, which was largely thought to be unique to osteoclasts...
  46. Maschalidi S, Hässler S, Blanc F, Sepulveda F, Tohme M, Chignard M, et al. Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation. PLoS Pathog. 2012;8:e1002841 pubmed publisher
    ..Thus, AEP activity is critical for TLR7 processing, opening new possibilities for the treatment of influenza and TLR7-dependent inflammatory diseases. ..
  47. Lange A, Yutzey K. NFATc1 expression in the developing heart valves is responsive to the RANKL pathway and is required for endocardial expression of cathepsin K. Dev Biol. 2006;292:407-17 pubmed
    ..of RANKL signal transduction including RANKL, its receptor RANK, and the downstream remodeling enzyme cathepsin K (Ctsk) are expressed in the heart during valve remodeling and colocalize with NFATc1 in developing valve ..
  48. Pennypacker B, Shea M, Liu Q, Masarachia P, Saftig P, Rodan S, et al. Bone density, strength, and formation in adult cathepsin K (-/-) mice. Bone. 2009;44:199-207 pubmed publisher
    b>Cathepsin K (CatK) is a cysteine protease expressed predominantly in osteoclasts, that plays a prominent role in degrading Type I collagen...
  49. Lamothe B, Lai Y, Xie M, Schneider M, Darnay B. TAK1 is essential for osteoclast differentiation and is an important modulator of cell death by apoptosis and necroptosis. Mol Cell Biol. 2013;33:582-95 pubmed publisher
    ..To our knowledge, we are the first to report that mice in which TAK1 has been conditionally deleted in osteoclasts develop osteopetrosis. ..
  50. Ferron M, Settembre C, Shimazu J, LaCombe J, Kato S, Rawlings D, et al. A RANKL-PKC?-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts. Genes Dev. 2013;27:955-69 pubmed publisher
    ..Altogether, these results uncover a RANKL-dependent signaling pathway taking place in differentiated osteoclasts and culminating in the activation of TFEB to enhance lysosomal biogenesis-a necessary step for proper bone resorption. ..
  51. Morko J, Kiviranta R, Mulari M, Ivaska K, Vaananen H, Vuorio E, et al. Overexpression of cathepsin K accelerates the resorption cycle and osteoblast differentiation in vitro. Bone. 2009;44:717-28 pubmed publisher
    ..The present study describes the intracellular mechanisms by which overexpression of cathepsin K in osteoclasts results in enhanced bone resorption...
  52. Boskey A, Gelb B, Pourmand E, Kudrashov V, Doty S, Spevak L, et al. Ablation of cathepsin k activity in the young mouse causes hypermineralization of long bone and growth plates. Calcif Tissue Int. 2009;84:229-39 pubmed publisher
    b>Cathepsin K deficiency in humans causes pycnodysostosis, which is characterized by dwarfism and osteosclerosis...
  53. Miyauchi Y, Sato Y, Kobayashi T, Yoshida S, Mori T, Kanagawa H, et al. HIF1α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis. Proc Natl Acad Sci U S A. 2013;110:16568-73 pubmed publisher
    ..Oral administration of a HIF1α inhibitor protected Ovx mice from osteoclast activation and bone loss. Thus, HIF1α represents a promising therapeutic target in osteoporosis. ..
  54. Hirose J, Masuda H, Tokuyama N, Omata Y, Matsumoto T, Yasui T, et al. Bone resorption is regulated by cell-autonomous negative feedback loop of Stat5-Dusp axis in the osteoclast. J Exp Med. 2014;211:153-63 pubmed publisher
    ..The results suggest that Stat5 negatively regulates the bone-resorbing function of osteoclasts by promoting Dusp1 and Dusp2 expression, and IL-3 promotes Stat5 activation in osteoclasts. ..
  55. Jacome Galarza C, Soung D, Adapala N, Pickarski M, Sanjay A, Duong L, et al. Altered hematopoietic stem cell and osteoclast precursor frequency in cathepsin K null mice. J Cell Biochem. 2014;115:1449-57 pubmed publisher
    b>Cathepsin K (CatK) is a lysosomal cysteine protease necessary for bone resorption by osteoclasts (OCs), which originate from myeloid hematopoietic precursors...
  56. Parker I, Roberts L, Hansen L, Gleason R, Sutliff R, Platt M. Pro-atherogenic shear stress and HIV proteins synergistically upregulate cathepsin K in endothelial cells. Ann Biomed Eng. 2014;42:1185-94 pubmed publisher
    ..we have shown synergism between HIV proteins and pro-atherogenic shear stress to increase endothelial cell expression of the powerful protease cathepsin K, and may implicate this protease in accelerated CVD in people living with HIV.
  57. Sinnesael M, Jardí F, Deboel L, Laurent M, Dubois V, Zajac J, et al. The androgen receptor has no direct antiresorptive actions in mouse osteoclasts. Mol Cell Endocrinol. 2015;411:198-206 pubmed publisher
    ..To examine whether AR in osteoclasts directly suppresses bone resorption, we crossed AR-floxed with cathepsin K-Cre mice...
  58. Wilson S, Peters C, Saftig P, Bromme D. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009;284:2584-92 pubmed publisher
    b>Cathepsin K is responsible for the degradation of type I collagen in osteoclast-mediated bone resorption. Collagen fragments are known to be biologically active in a number of cell types...
  59. Combs M, Yutzey K. VEGF and RANKL regulation of NFATc1 in heart valve development. Circ Res. 2009;105:565-74 pubmed publisher
    ..As ECCs mature, RANKL (receptor activator of nuclear factor kappaB ligand) and the ECM-remodeling enzyme cathepsin K (CtsK) are expressed by ECC endothelial cells...
  60. Wilson S, Hashamiyan S, Clarke L, Saftig P, Mort J, Dejica V, et al. Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities. Am J Pathol. 2009;175:2053-62 pubmed publisher
    ..As GAGs can regulate the collagenolytic activity of the major osteoclastic protease cathepsin K, we investigated the presence and activity of cathepsin K and its co-localization with GAGs in ..
  61. Mizoguchi F, Izu Y, Hayata T, Hemmi H, Nakashima K, Nakamura T, et al. Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem. 2010;109:866-75 pubmed publisher
    ..We specifically knocked out Dicer in osteoclasts by crossing Dicer flox mice with cathepsin K-Cre knock-in mice. Dicer deficiency in osteoclasts decreased the number of osteoclasts (N...
  62. Takeshita S, Fumoto T, Matsuoka K, Park K, Aburatani H, Kato S, et al. Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J Clin Invest. 2013;123:3914-24 pubmed publisher
    ..These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling. ..
  63. Schulze J, Bickert T, Beil F, Zaiss M, Albers J, Wintges K, et al. Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells. J Bone Miner Res. 2011;26:704-17 pubmed publisher
    ..Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. ..
  64. Knaapi J, Lukkarinen H, Kiviranta R, Vuorio E, Kääpä P. Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn mice. Exp Lung Res. 2011;37:408-18 pubmed publisher
    b>Cathepsin K (CatK) is a potent collagenase and elastase and may be involved in the development of neonatal bronchopulmonary dysplasia...
  65. Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, et al. Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat Med. 2012;18:405-12 pubmed publisher
    ..Our results suggest that the Wnt5a-Ror2 pathway is crucial for osteoclastogenesis in physiological and pathological environments and represents a therapeutic target for bone diseases, including arthritis. ..
  66. Jiang T, Liu F, Wang W, Jiang X, Wen X, Hu K, et al. Distribution of Cathepsin K in Late Stage of Tooth Germ Development and Its Function in Degrading Enamel Matrix Proteins in Mouse. PLoS ONE. 2017;12:e0169857 pubmed publisher
    b>Cathepsin K (CTSK) is a member of cysteine proteinase family, and is predominantly expressed in osteoclastsfor degradationof bone matrix proteins...
  67. Wei W, Zeve D, Suh J, Wang X, Du Y, Zerwekh J, et al. Biphasic and dosage-dependent regulation of osteoclastogenesis by ?-catenin. Mol Cell Biol. 2011;31:4706-19 pubmed publisher
    ..Importantly, these findings suggest that Wnt activation is a more effective treatment for skeletal fragility than previously recognized that confers dual anabolic and anti-catabolic benefits. ..
  68. Zhang D, Huang C, Yang C, Liu R, Wang J, Niu J, et al. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts. Respir Res. 2011;12:154 pubmed publisher
    ..These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-?..
  69. Ibrahim S, Koczan D, Thiesen H. Gene-expression profile of collagen-induced arthritis. J Autoimmun. 2002;18:159-67 pubmed
    ..e. MHC class I, II, Basigin, FAP, Cathepsin K, CD 53, RAF1, glucagon, and retinal taurine transporter...
  70. Schurigt U, Hummel K, Petrow P, Gajda M, Stöckigt R, Middel P, et al. Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor-transgenic mice. Arthritis Rheum. 2008;58:422-34 pubmed publisher
    b>Cathepsin K is believed to have an eminent role in the pathologic resorption of bone. However, several studies have shown that other proteinases also participate in this process...
  71. Pang M, Martinez A, Fernandez I, Balkan W, Troen B. AP-1 stimulates the cathepsin K promoter in RAW 264.7 cells. Gene. 2007;403:151-8 pubmed
    b>Cathepsin K (CTSK) is a secreted protease that plays an essential role in osteoclastic bone resorption, and CTSK levels increase with osteoclast differentiation and activation, a process that is controlled by a complex physiological ..
  72. Tsuji Takechi K, Negishi Koga T, Sumiya E, Kukita A, Kato S, Maeda T, et al. Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development. Proc Natl Acad Sci U S A. 2012;109:2561-6 pubmed publisher
    ..Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment. ..
  73. Morko J, Kiviranta R, Joronen K, Saamanen A, Vuorio E, Salminen Mankonen H. Spontaneous development of synovitis and cartilage degeneration in transgenic mice overexpressing cathepsin K. Arthritis Rheum. 2005;52:3713-7 pubmed
    Several recent studies have demonstrated that cathepsin K, a proteolytic enzyme capable of degrading native fibrillar collagen, is overexpressed in osteoarthritic cartilage and inflamed synovial tissue...
  74. Godat E, Lecaille F, Desmazes C, Duchêne S, Weidauer E, Saftig P, et al. Cathepsin K: a cysteine protease with unique kinin-degrading properties. Biochem J. 2004;383:501-6 pubmed
    ..Wild-type fibroblast lysates from mice, by contrast with cathepsin K-deficient lysates, hydrolysed BK (bradykinin), and released two metabolites, BK-(1-4) and BK-(5-9)...
  75. Sol Church K, Frenck J, Mason R. Mouse cathepsin M, a placenta-specific lysosomal cysteine protease related to cathepsins L and P. Biochim Biophys Acta. 2000;1491:289-94 pubmed
    ..This is in contrast to human cathepsins L and V, which probably resulted from a gene duplication after divergence of mammalian species. ..
  76. Lips K, Kneffel M, Willscheid F, Mathies F, Kampschulte M, Hartmann S, et al. Altered ultrastructure, density and cathepsin K expression in bone of female muscarinic acetylcholine receptor M3 knockout mice. Int Immunopharmacol. 2015;29:201-7 pubmed publisher
    ..In M3R-KO, the number of osteoclasts as well as the cathepsin K mRNA expression was increased. Osteoclasts of M3R-KO showed an estimated increase in cytoplasmic vesicles...
  77. Ito Y, Teitelbaum S, Zou W, Zheng Y, Johnson J, Chappel J, et al. Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL/M-CSF signaling and osteoclast polarization. J Clin Invest. 2010;120:1981-93 pubmed publisher
    ..These data suggest that Cdc42 regulates osteoclast formation and function and may represent a promising therapeutic target for prevention of pathological bone loss. ..
  78. Podgorski I, Linebaugh B, Koblinski J, Rudy D, Herroon M, Olive M, et al. Bone marrow-derived cathepsin K cleaves SPARC in bone metastasis. Am J Pathol. 2009;175:1255-69 pubmed publisher
    ..Here, we investigated the involvement of cathepsin K in the progression of prostate tumors in the bone, which occurs both by direct degradation of bone matrix ..