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. 2022 May;28(4):1170-1180. doi: 10.1111/odi.13808. Epub 2021 Mar 9.
This study aimed to explore the effects of metformin on osteogenic differentiation of alveolar bone marrow mesenchymal stem cells (BMSCs) from type-2 diabetes mellitus (T2DM) patients (DM-BMSCs) and implant osseointegration in rats, screen the optimal concentration, and investigate whether metformin could protect against the adverse impact of T2DM on BMSC osteogenic capacity.
Different concentrations of metformin were administered to human-derived BMSCs and Wistar rats receiving implants. ALP detection, alizarin red staining, real-time RT-PCR and Western blotting were performed to detect osteogenesis and investigate the mechanism. Toluidine blue staining was performed to analyse bone-implant contact in rats.
Metformin increased implant osseointegration in a rat model and promoted the osteogenic capacity of DM-BMSCs via the AMPK/BMP/Smad signalling pathway, and 125 μM was the optimal concentration; however, concentrations over 200 µM, metformin showed an inhibitory effect on DM-BMSCs. Additionally, metformin at the optimal concentration (125 µM) identified in this study could compensate for the negative impacts of T2DM on the osteogenic differentiation of BMSCs.
Metformin can promote the osteogenesis of BMSCs from T2DM patients and osseointegration in rats, and it might be an effective drug for increasing the success rate of T2DM-associated implants.
本研究旨在探讨二甲双胍对 2 型糖尿病（T2DM）患者骨髓间充质干细胞（BMSCs）成骨分化及大鼠种植体骨整合的影响，筛选最佳浓度，并探讨二甲双胍是否能保护 T2DM 对 BMSC 成骨能力的不利影响。
将不同浓度的二甲双胍作用于人源性 BMSCs 和植入大鼠，通过碱性磷酸酶（ALP）检测、茜素红染色、实时 RT-PCR 和 Western blot 检测成骨情况，并探讨其作用机制。采用甲苯胺蓝染色分析大鼠种植体骨接触情况。
二甲双胍通过 AMPK/BMP/Smad 信号通路增加大鼠模型种植体的骨整合，并促进 DM-BMSCs 的成骨能力，125μM 为最佳浓度；但浓度超过 200μM 时，二甲双胍对 DM-BMSCs 表现出抑制作用。此外，本研究中确定的最佳浓度（125μM）二甲双胍可补偿 T2DM 对 BMSCs 成骨分化的负面影响。
二甲双胍可促进 T2DM 患者 BMSCs 的成骨作用和大鼠种植体的骨整合，可能是提高 T2DM 相关种植体成功率的有效药物。
