The effect of liraglutide on the proliferation, migration, and osteogenic differentiation of human periodontal ligament cells

J Periodontal Res. 2019 Apr;54(2):106-114. doi: 10.1111/jre.12607. Epub 2018 Sep 12.

Abstract

Objective: Liraglutide (LIRA) is a novel antidiabetic therapy that may have anti-inflammatory and bone protective effects. Thus, we studied the potential therapeutic effect of LIRA on periodontitis by assessing the effects of LIRA on the proliferation, migration, inflammation, and osteogenic differentiation of human periodontal ligament cells (hPDLCs) after LPS stimulation.

Material and methods: The expression of glucagon like-peptide 1 receptor (GLP-1R) was measured using qRT-PCR. HPDLCs proliferation after LIRA were analyzed using MTT assays. Cell migration was quantified using a wound-healing assay. The expression of inflammatory (IL-6 and TNF-α) was measured by qRT-PCR and ELISA in hPDLCs. The effect of LIRA on the mineralization potential of hPDLCs was assessed by alizarin red S staining. Furthermore, the expression of Runx2 and ALP was measured by qRT-PCR and Western blot in hPDLCs.

Results: GLP-1R mRNA was present on hPDLCs, and LIRA increased the expression of GLP-1R mRNA. When cultured with 25, 50, 75, 100 and 125 nM LIRA for 24 h, hPDLCs proliferation was enhanced in a dose-dependent manner (P < 0.05), and 100 nM was optimal. LIRA promoted hPDLCs migration in a time-dependent manner. LPS significantly increased the expression of IL-6 and TNF-α (P < 0.01), decreased the formation of mineralization nodes (P < 0.01), and inhibited the expression of ALP and Runx2 (P < 0.05). LIRA treatment blocked the expression of IL-6 and TNF-α (P < 0.01), increased the formation of mineralization nodes (P < 0.01), and enhanced the expression of ALP and Runx2 (P < 0.05).

Conclusion: LIRA can enhance the proliferation, migration, and osteogenic differentiation of hPDLCs and inhibit the inflammatory response. Thus, LIRA may have potential therapeutic use as an adjuvant treatment for human periodontitis, and this effect is independent of hypoglycemic activity.

Keywords: LIRA; LPS; hPDLCs; inflammatory factors; osteogenesis factors.

MeSH terms

  • Biomarkers / metabolism
  • Cell Differentiation / drug effects*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Inflammation
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Liraglutide / pharmacology*
  • Liraglutide / therapeutic use
  • Osteogenesis / drug effects*
  • Periodontal Ligament / cytology*
  • Periodontitis / diagnosis
  • Periodontitis / drug therapy
  • Periodontitis / genetics
  • Periodontitis / pathology*
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Inflammation Mediators
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Liraglutide