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

Abstract

AbstractThe 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‐κB 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‐κB 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‐κB‐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‐κB 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‐κB was investigated. In parallel, QNZ and NF‐κB‐specific siRNA were used to inhibit NF‐κB. In vivo, the FABP4 WT mice had more significant NF‐κB activation than the KO mice. Dual inhibition of FABP4 and NF‐κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF‐κB in chondrocytes. The use of QNZ and NF‐κB‐siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF‐κB pathway.