title: Regulation of chondrocyte functions by transient receptor potential cation channel V6 in osteoarthritis.
abstract: Transient receptor potential vanilloid (TRPV) channels function to maintain the dynamic balance of calcium signaling and calcium metabolism in bones. The goal of this study was to determine the potential role of TRPV6 in regulation of chondrocytes. The level of TRPV6 expression was analyzed by western blot in articular cartilage derived from the knee joints of osteoarthritis (OA) rat models and OA patients. Bone structure and osteoarthritic changes in the knee joints of TRPV6 knockout mice were examined using micro-computed and histological analysis at the age of 6 and 12 months old. Furthermore, to investigate the effects of TRPV6 on chondrocyte extracellular matrix secretion, the release of matrix degrading enzymes, cell proliferation, and apoptosis, we decreased and increased TRPV6 expression in chondrocytes with lentiviral constructs encoding shRNA targeting TRPV6 and encoding TRPV6, respectively. The results showed that the level of TRPV6 expression in an OA rat model was markedly down-regulated. TRPV6 knockout mice showed severe osteoarthritis changes, including cartilage fibrillation, eburnation, and loss of proteoglycans. In addition, deficiency of TRPV6 clearly affected chondrocyte function, such as extracellular matrix secretion, the release of matrix degrading enzymes, cell proliferation, and apoptosis. Taken together, our results implicated that TRPV6 channel, as a chondro-protective factor, was involved in the pathogenesis of OA.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lei
authors.identifier: http://orcid.org/0000-0001-5143-3234
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tianwen
authors.identifier: http://orcid.org/0000-0002-2495-7590
authors.initials: T
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D020219:Chondrogenesis; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D055114:X-Ray Microtomography
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C120776:TRPV6 channel; C422827:TRPV6 protein, human; C446923:Trpv6 protein, mouse
keywords: TRPV6; cartilage extracellular matrix; chondrocyte; osteoarthritis