Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-b signaling pathway

The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF-kappa B in FABP4-induced OA. In the in vivo study, four pairs of 12-week-old male FABP4 knockout (KO) and wild-type (WT) mice were included. The activation of NF-kappa B was assessed. In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-kappa B-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF-kappa B activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF-kappa B was investigated. In parallel, QNZ and NF-kappa B-specific siRNA were used to inhibit NF-kappa B. In vivo, the FABP4 WT mice had more significant NF-kappa B activation than the KO mice. Dual inhibition of FABP4 and NF-kappa B alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF-kappa B in chondrocytes. The use of QNZ and NF-kappa B-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-kappa B pathway.