Sitagliptin regulates the AMPK/NF-κB signaling pathway to alleviate lipopolysaccharide-induced inflammatory responses and promote osteogenic differentiation in rat bone marrow mesenchymal stem cells

OBJECTIVE: This study aimed to explore the impact of sitagliptin on the inflammatory response and osteogenic differentiation in lipopolysaccharide (LPS)-stimulated rat bone marrow mesenchymal stem cells (BMSCs) and to clarify the underlying mechanisms of action. DESIGN: In vitro-cultured rat BMSCs were identified, treated with a range of sitagliptin doses, and assessed with a cell counting kit-8 assay to quantify viability. The expression of proteins and genes relevant to inflammation and osteogenesis was measured using enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction techniques. The osteogenic differentiation ability of rat BMSCs was analyzed by alkaline phosphatase staining, alkaline phosphatase activity assay, and alizarin red s staining. Adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-kappa B (NF-κB) signaling pathway activation was detected through western blotting. RESULTS: High but not low sitagliptin concentrations significantly suppressed cellular viability. Sitagliptin dose-dependently inhibited LPS-induced rat BMSCs inflammatory responses while facilitating their osteogenic differentiation. It also activated AMPK pathway signaling while suppressing NF-κB activity. AMPK inhibitor treatment of rat BMSCs partially reversed these beneficial effects of sitagliptin on inflammation and osteogenesis. CONCLUSIONS: Sitagliptin suppresses rat BMSCs inflammation while promoting osteogenesis through the modulation of AMPK/NF-κB signaling activity, thereby mitigating the functional impairment of rat BMSCs under inflammatory microenvironmental conditions.