Fatty acid binding protein 4 induces osteogenesis and angiogenesis as pathogenesis of metabolic osteoarthritis

The pathogenesis of osteoarthritis (OA) is not yet fully elucidated. FABP4 plays a role in the occurrence of metabolic OA, however, the mechanism remains unclear. The purpose of this study was to further explore the mechanism by which FABP4 mediates the occurrence of metabolic OA.

In vivo, FABP4 knockout mice (KO) and wild-type littermates (WT) were fed with high-fat diet (HFD) for 3 and 6 months. WT mice were fed with HFD and treated with FABP4 inhibitor BMS309403 (30 mg/kg/d) or vehicle for 6 months. Knee cartilage degenerative changes and subchondral bone changes were assessed. In vitro, FABP4 was used to stimulate mouse bone marrow mesenchymal stem cells (mMSCs) and endothelial progenitor cells (EPCs). Osteogenesis and angiogenesis were assessed.

In vivo, knocking out of FABP4 and pharmaceutical inhibition of FABP4 significantly alleviated subchondral bone sclerosis and type H vessel formation in mice fed with HFD, and was significantly associated with osteogenesis and angiogenesis. In vitro, FABP4 promotes the differentiation of MSCs into osteoblasts through activation of the PI3K/Akt signaling pathway, and promotes the expression of osteogenesis-related proteins. FABP4 also promotes endothelial cell migration, tube formation, and wound healing through activating the PI3K/Akt pathway.

This study suggests that FABP4 induced subchondral bone osteogenesis and angiogenesis. The PI3K-Akt signaling pathway plays a critical role in both processes. Inhibition of FABP4 may serve as a potential therapeutic approach for metabolic OA.