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.