2. Academic Validation
  3. Liraglutide Promoted Osteogenic Differentiation of Dental Pulp Stem Cells via H3K18 Lactylation-Dependent DSPP Activation

Liraglutide Promoted Osteogenic Differentiation of Dental Pulp Stem Cells via H3K18 Lactylation-Dependent DSPP Activation

  • Tissue Eng Regen Med. 2026 Jun;23(4):573-582. doi: 10.1007/s13770-026-00801-9.
Ruixue Li # 1,  Jing Zhang # 2,  Xixi Song 1,  Lulu Han 1,  Mingyan Yao 3
Affiliations

Affiliations

  • 1 Department of Endocrinology, Baoding No. 1 Central Hospital, Changcheng North Street, No.320, Lianchi District, Baoding, 071000, China.
  • 2 Department of Cardiology, Affiliated Hospital of Hebei University, Baoding, China.
  • 3 Department of Endocrinology, Baoding No. 1 Central Hospital, Changcheng North Street, No.320, Lianchi District, Baoding, 071000, China. [email protected].
  • # Contributed equally.
PMID: 41849034 DOI: 10.1007/s13770-026-00801-9
Abstract

Background: Dental pulp stem cells (DPSCs) are critical for periodontal tissue regeneration, yet their therapeutic potential is limited by suboptimal osteogenic differentiation. Liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, exhibits anti-inflammatory and bone-protective properties. This study aimed to investigate the modulatory effects of LIRA on DPSCs proliferation and osteogenic differentiation.

Methods: DPSCs were treated with LIRA to assess proliferation and osteogenic differentiation using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine staining, Alkaline Phosphatase (ALP), and alizarin red S (ARS) assays. Histone lactylation levels (total lactylation and H3K18la) were quantified by Western blot. Chromatin immunoprecipitation (ChIP) and dual-luciferase assays evaluated H3K18la enrichment at the dentin sialophosphoprotein (DSPP) promoter. DSPP overexpression was used in rescue experiments to validate the role of the H3K18la-DSPP axis.

Results: LIRA significantly enhanced DPSC proliferation and osteogenic differentiation, as evidenced by increased ALP activity, mineralization nodules, and upregulated osteogenic markers (DMP1, DSPP, RUNX2, OCN, OPN). LIRA elevated global lactylation and H3K18la levels, with ChIP assays showing H3K18la enrichment specifically at the DSPP promoter. Dual-luciferase and RT-qPCR confirmed LIRA-induced DSPP transcriptional activation. Oxamate reversed LIRA's effects, while Nala amplified them. DSPP overexpression rescued oxamate-mediated suppression of osteogenesis, confirming the H3K18la-DSPP regulatory mechanism.

Conclusion: This study demonstrates that LIRA promotes DPSC osteogenesis via histone lactylation-mediated DSPP transcriptional activation. The H3K18la-DSPP axis represents a novel metabolic-epigenetic pathway for enhancing periodontal regeneration.

Keywords

DSPP; Dental pulp stem cells; H3K18la; Liraglutide; Osteogenic differentiation.

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