WISP3 suppresses insulin-like growth factor signaling in human chondrocytes.
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.
Cui
Rong-Rong
RR
Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Huang
Jiao
J
Yi
Lu
L
Xie
Hui
H
Zhou
Hou-De
HD
Yuan
Ling-Qing
LQ
Wang
Min
M
Peng
Yi-Qun
YQ
Luo
Xiang-Hang
XH
Liao
Er-Yuan
EY
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
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