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

  • Arch Oral Biol. 2025 Jul:175:106253. doi: 10.1016/j.archoralbio.2025.106253.
Xi Yao  1 ,  Min Liu  2 ,  Pin Wang  3
Affiliations
  • 1. Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Department of Oral prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Institute of Stomatology, Southwest Medical University, Luzhou, China.
  • 2. Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Department of Oral prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Institute of Stomatology, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
  • 3. Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Department of Oral prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China; Institute of Stomatology, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
PMID: 40215713 DOI: 10.1016/j.archoralbio.2025.106253
Abstract

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.

Keywords
AMPK/NF-κB signaling pathway; Bone marrow mesenchymal stem cells; Inflammatory response; Osteogenic differentiation; Peri-implantitis; Sitagliptin.
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