title: IGFBP-3 may trigger osteoarthritis by inducing apoptosis of chondrocytes through Nur77 translocation.
abstract: Osteoarthritis is not an uncommon disease worldwide and it is characterized by chondrocytes apoptosis in articular cartilages. Previous researches had discovered that insulin-like growth factor binding protein-3 (IGFBP-3) was abundant inside the osteoarthritic cartilages and the more IGFBP-3, the worse of osteoarthritis. However, there is still little knowledge of the association between the onset of osteoarthritis and the yield of IGFBP-3 in cartilages. In consideration of the apoptotic effect of IGFBP-3 on other types of cells, we had hypothesized that IGFBP-3 may induce the chondrocytes apoptosis, which was highly considered as the origin of the osteoarthritis. Exposing the cultured chondrocytes to exogenous recombinant IGFBP-3, we were able to observed the apoptotic chondrocytes under microscope and figured out an increased proportion (P<0.05) of them by both CCK-8 assay and flow cytometry. Under laser confocal microscope, we also found that the apoptosis of chondrocytes induced by IGFBP-3 were committed to the nucleus-mitochondria translocation of Nur77, which is nuclear protein, and this phenomena was similar as the one described in malignant cells only. In conclusion, our work suggested that IGFBP-3 may trigger osteoarthritis by inducing the chondrocytes apoptotic through nucleus-mitochondria translocation of Nur77.
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital of Wuhan University Wuhan, Hubei Province, China.
authors.forename: Zhun
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University Wuhan, Hubei Province, China.
authors.forename: Hao-Huan
authors.initials: HH
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1
keywords: IGFBP-3; Insulin-like growth factor binding protein-3; Nur77; chondrocytes; nucleus-mitochondria translocation