Fibroblast growth factor 8 (FGF8) up-regulates gelatinase expression in chondrocytes through nuclear factor-κB p65

Abstract

Gelatinases, namely MMP2 and MMP9, are involved in the natural turnover of articular cartilage, as well as the loss of the cartilage matrix in osteoarthritis (OA). Studies have reported that fibroblast growth factor 8 (FGF8) promoted the degradation of cartilage in OA. In the present study, we predicted that FGF8 promoted chondrocyte expression and secretion of gelatinases by activating NF-κB p65 signaling. Primary chondrocytes from C57 mice were cultured with recombinant FGF8. RNA sequencing was employed to explore the gene expression changes of gelatinases. Gelatin zymography was used to determine the activation of gelatinases. Western blot was used to investigate the expression of the gelatinases and NF-κB p65 signaling pathways, and immunofluorescence staining and NF-κB inhibitor assays were performed to confirm the activation of NF-κB p65 signaling. FGF8 could increase the expression and activity of gelatinases in primary chondrocytes. And FGF8-induced expression of gelatinases was regulated through activation of NF-κB signaling with acetylated p65 accumulating in the cell nucleus. We further found that the NF-κB inhibitor, BAY 11-7082, could suppress up-regulation of gelatinase induced by FGF8. FGF8 enhanced the expression and activity of MMP2 and MMP9 in chondrocytes via NF-κB p65 signaling.