Effect of Irisin on the Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells

ABSTRACT To investigate the effect of irisin on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in a femoral defect model. Rat BMSCs were treated with irisin in vitro, and osteogenic markers were analysed using reverse transcription quantitative polymerase chain reaction. In vivo, irisin‐loaded composite scaffolds or blank scaffolds were implanted into rat femoral defects ( n = 6 per group). Bone repair was assessed by micro‐computed tomography, haematoxylin and eosin staining, and immunohistochemistry after 8 weeks. Irisin treatment significantly enhanced calcium nodule formation, as evidenced by increased staining intensity, size and number in both Alizarin Red and von Kossa assays. At the molecular level, Sost expression was markedly downregulated, whereas ALP , Lrp5 , BMP2 and Smad1 were significantly upregulated at both mRNA levels (all p < 0.001). In vivo, rats implanted with irisin‐composite scaffolds showed substantially improved bone repair, with higher bone volume fraction, bone mineral density and cortical bone volume compared with controls. Irisin promotes the osteogenic differentiation of rat BMSCs and accelerates bone regeneration in a critical‐sized femoral defect model, potentially through suppression of Sost and subsequent activation of the Wnt and BMP signalling pathways. These findings highlight the therapeutic potential of irisin for bone tissue engineering applications.