RAI3 knockdown enhances osteogenic differentiation of bone marrow mesenchymal stem cells via STAT3 signaling pathway

Abstract

Bone marrow mesenchymal stem cells (BMSCs), which have multipotential differentiation and self-renewal ability, have been becoming an attractive source of seed cells for bone tissue engineering. Nonetheless, the precise underlying mechanisms of osteogenesis of BMSCs have not been fully understood. Retinoic acid-induced gene 3 (RAI3) has been found to play important roles in mesenchymal stem cells (MSCs) adipogenesis in our previous study. However, its function in the osteogenic differentiation of BMSCs remains unknown. In this study, we found that RAI3 was significantly reduced in osteogenically differentiated BMSCs; RAI3 knockdown promoted osteogenesis of BMSCs both in vitro and in vivo. Moreover, we found RAI3 knockdown significantly upregulated the expression level of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and AG-490 which can inhibit the STAT3 signaling reversed the enhancing effect of RAI3 knockdown on the osteogenic differentiation of BMSCs. These results suggest that RAI3 plays important roles in BMSCs osteogenesis with an involvement of the STAT3 signaling, which might open a new avenue to explore BMSCs osteogenesis for the application of BMSCs in bone regeneration.

Keywords: Bone marrow mesenchymal stem cells; Bone tissue engineering; Osteogenic differentiation; RAI3; STAT3 signaling.