title: WISP3 suppresses insulin-like growth factor signaling in human chondrocytes.
abstract: WISP3 is essential for maintaining cartilage integrity mainly by regulating the expression of collagen II, and mutations of WISP3 linked to spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) can compromise this function and lead to cartilage loss. The aim of this study was to evaluate the effect of WISP3 on insulin-like growth factor (IGF) signaling in human chondrocytes, investigate whether WISP3 up-regulates collagen II through the IGF signaling pathway, and compare IGF signaling between wild-type and mutant WISP3. Experimental results suggest that WISP3 up-regulates collagen II expression and inhibits the activation of IGF-IR, IRS-1, and ERK kinase in human chondrocytes, and mutation of WISP3 augments IGF signaling in human chondrocytes. In addition to the IGF signaling pathway, WISP3 might up-regulate collagen II expression through an IGF-independent signaling cascade.
authors.affiliation: Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Cui
authors.forename: Jiao
authors.initials: J
authors.lastname: Huang
authors.forename: Lu
authors.initials: L
authors.lastname: Yi
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Peng
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
mesh_terms: D055511:CCN Intercellular Signaling Proteins; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D017526:Receptor, IGF Type 1