Liraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro.

Abstract

As a GLP-1 receptor agonist widely used in treating type 2 diabetes, liraglutide shows potential applications in bone tissue engineering. This study investigated liraglutide's direct effects on rat bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and its regulatory mechanism through macrophage polarization. Results showed that liraglutide significantly enhanced BMSC migration and osteogenic differentiation. Additionally, liraglutide markedly inhibited M1 macrophage polarization induced by LPS and IFN-γ, reducing inflammatory factors CXCL9 and TNF-α secretion, possibly by partially reversing M1 macrophage regulatory signals (AMPK and NF-κB pathways). Compared to M1 macrophage-conditioned medium (M1-CM), conditioned medium from liraglutide-treated macrophages showed stronger promotion of BMSC osteogenic differentiation, though this effect was reversed by CXCL9 addition. The study demonstrates that liraglutide enhances BMSC osteogenic capacity both directly and by inhibiting M1 macrophage polarization and CXCL9 secretion, offering a new therapeutic option for severe bone defects with inflammatory responses.