FSTL1 Promotes Inflammatory Reaction and Cartilage Catabolism through Interplay with NFκB Signaling Pathways in an In Vitro ONFH Model

Osteonecrosis of the femoral head (ONFH) usually occurs in young people and is closely associated with autoimmune reactions. Follistatin-like 1 (FSTL1) was recently proven to participate in several inflammation-related diseases. The role of FSTL1 in ONFH is still unclear. Serum levels of FSTL1 were not significantly different in ONFH patients and healthy individuals. In contrast, elevated expression levels of FSTL1 were observed in degraded cartilage and synovial fluid in ONFH patients and in a cultured human primary chondrocyte model treated with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). Suppression of FSTL1 by FSTL1-siRNA downregulated the inflammatory response mediated by IL-1 beta or TNF-alpha in cultured human chondrocytes. In a human cartilage culture model, FSTL1 promoted the production of inflammatory cytokines and cartilage degradation enzymes. The activation of NF kappa B signaling pathway was detected in degenerated cartilage from ONFH patients and in FSTL1-treated chondrocytes. Additionally, administration of an NF kappa B inhibitor (JSH-23) significantly reduced the overexpression of inflammatory cytokines and protein degradation enzymes induced by FSTL1 and maintained the level of major cartilage matrix components (aggrecan and collagen II). In summary, FSTL1 was involved in the degeneration progression of the ONFH and might provide a novel direction for treating and curing ONFH.