Wang Yao, Sun Yujie, Yang Bo, Li Jun, Liang Chao
Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.
Oral Dis. 2024 Nov;30(8):5160-5174. doi: 10.1111/odi.14931. Epub 2024 Mar 19.
To investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant-bone integration in rats with T2DM.
Extracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT-PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro-CT. Implant-bone integration in rats was investigated via toluidine blue staining.
Liraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10 mol/L. At concentrations higher than 10 mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10 mol/L liraglutide, BMSCs and diabetes mellitus-bone marrow stromal cells (DM-BMSCs) showed optimal osteogenesis. Liraglutide promoted implant-bone integration and new bone formation in Wistar and GK rats.
Liraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.
探讨利拉鲁肽对人牙槽骨骨髓间充质干细胞(BMSCs)成骨作用的影响以及对2型糖尿病大鼠种植体与骨结合的影响。
从接受胰岛素治疗的糖尿病患者牙槽中提取BMSCs。用不同浓度的利拉鲁肽处理BMSCs。通过碱性磷酸酶(ALP)检测、ALP染色、茜素红S染色、蛋白质免疫印迹法和逆转录-聚合酶链反应(RT-PCR)研究成骨作用及其潜在机制。在种植后给Wistar大鼠和GK大鼠注射利拉鲁肽,通过显微计算机断层扫描(micro-CT)分析种植体周围新骨形成情况。通过甲苯胺蓝染色研究大鼠种植体与骨的结合情况。
利拉鲁肽通过骨形态发生蛋白2(BMP2)/Smad/Runx2信号通路增强BMSCs的成骨作用。促进成骨的利拉鲁肽最佳浓度为10μmol/L。浓度高于10μmol/L时,利拉鲁肽对BMSCs有负面影响。在10μmol/L利拉鲁肽浓度下,BMSCs和糖尿病骨髓基质细胞(DM-BMSCs)表现出最佳成骨作用。利拉鲁肽促进Wistar大鼠和GK大鼠种植体与骨的结合及新骨形成。
利拉鲁肽不仅促进血糖正常个体BMSCs的成骨作用,还增强接受胰岛素治疗的糖尿病患者BMSCs的成骨作用,并增强大鼠的骨整合。