School of Stomatology, Lanzhou University, Lanzhou, China.
J Periodontal Res. 2019 Apr;54(2):106-114. doi: 10.1111/jre.12607. Epub 2018 Sep 12.
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.
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.
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).
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.
利拉鲁肽（LIRA）是一种新型的抗糖尿病治疗药物，可能具有抗炎和护骨作用。因此，我们通过评估 LIRA 对 LPS 刺激后人牙周韧带细胞（hPDLCs）的增殖、迁移、炎症和成骨分化的影响，研究了 LIRA 治疗牙周炎的潜在疗效。
通过 qRT-PCR 测定胰高血糖素样肽 1 受体（GLP-1R）的表达。用 MTT 法分析 LIRA 处理后 hPDLCs 的增殖情况。用划痕愈合实验定量测定细胞迁移。通过 qRT-PCR 和 ELISA 测定 hPDLCs 中炎症因子（IL-6 和 TNF-α）的表达。通过茜素红 S 染色评估 LIRA 对 hPDLCs 矿化潜能的影响。此外，通过 qRT-PCR 和 Western blot 测定 hPDLCs 中 Runx2 和 ALP 的表达。
hPDLCs 存在 GLP-1R mRNA，LIRA 增加了 GLP-1R mRNA 的表达。当用 25、50、75、100 和 125 nM LIRA 培养 24 h 时，hPDLCs 的增殖呈剂量依赖性增强（P<0.05），100 nM 时效果最佳。LIRA 呈时间依赖性促进 hPDLCs 迁移。LPS 显著增加了 IL-6 和 TNF-α 的表达（P<0.01），减少了矿化结节的形成（P<0.01），并抑制了 ALP 和 Runx2 的表达（P<0.05）。LIRA 处理阻断了 IL-6 和 TNF-α 的表达（P<0.01），增加了矿化结节的形成（P<0.01），并增强了 ALP 和 Runx2 的表达（P<0.05）。
LIRA 可增强 hPDLCs 的增殖、迁移和成骨分化，并抑制炎症反应。因此，LIRA 可能作为人类牙周炎的辅助治疗具有潜在的治疗用途，且这种作用与降血糖活性无关。
