Analysis of the role of irisin receptor signaling in regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells

The study aimed to explore the role of the irisin receptor (integrin αVβ5) signaling pathway in obesity-induced osteoporosis and its potential mechanism. The integrin αVβ5 gene of bone marrow mesenchymal stem cells (BMSCs) was silenced and overexpressed, and the cells were exposed to irisin treatment and mechanical stretch. Mouse models of obesity were established by feeding mice a high-fat diet, and 8-week caloric restriction/aerobic exercise regimens were implemented. The results showed that after silencing the integrin αVβ5, the osteogenic differentiation of BMSCs was significantly reduced. While overexpression of the integrin αVβ5 increased the osteogenic differentiation of BMSCs. Besides, mechanical stretch promoted the osteogenic differentiation of BMSCs. Obesity did not affect integrin αVβ5 expression in the bone, but it downregulated the expression of irisin and osteogenic factors, upregulated the expression of adipogenic factors, increased bone marrow fat, reduced bone formation, and destroyed the bone microstructure. Caloric restriction, exercise, and a combined regimen reversed these effects and improved obesity-induced osteoporosis, with the combined treatment exhibiting the most potent effect. This study confirms that the irisin receptor signaling pathway has a significant part in transmitting 'mechanical stress' and regulating 'osteogenic/adipogenic differentiation' of BMSCs via recombinant irisin, mechanical stretch, and overexpression/silencing of the integrin αVβ5 gene.