IGFBP-3 may trigger osteoarthritis by inducing apoptosis of chondrocytes through Nur77 translocation

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.