Department of Endocrinology, Wuhan Third Hospital, Wuhan University, Wuhan 430062, China.
Department of Cardiology, Wuhan Third Hospital, Wuhan University, Wuhan 430062, China.
Endocr Metab Immune Disord Drug Targets. 2023;23(8):1077-1086. doi: 10.2174/1871530323666230109124631.
Patients with type 2 diabetes mellitus (T2DM) are at high risk for osteoporosis. SIRT1 plays an important regulatory role in the occurrence and development of diabetes mellitus; however, it is still not clear whether SIRT1 is directly related to the osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) in T2DM patients.
We obtained BMSCs from patients with T2DM and healthy volunteers to determine the effect of SIRT1 expression on the osteogenic capacity of BMSCs. As a result, SIRT1 expression in BMSCs in T2DM was significantly lower compared to healthy volunteers, but the proliferative capacity of BMSCs in the T2DM group was not significantly different from that of healthy volunteers.
During osteogenic differentiation, the expression of SIRT1 in MSCs from T2DM patients was significantly decreased, and the osteogenic differentiation ability of MSCs from T2DM patients was significantly lower than healthy volunteers. After intervention with resveratrol, the expression of SIRT1 increased significantly, and the apoptotic rate of MSCs in T2DM patients decreased significantly. Moreover, resveratrol promoted osteoblast differentiation of MSCs.
Our study confirmed that the expression of SIRT1 is directly related to the osteogenic potential of BMSCs in patients with T2DM. Resveratrol promoted the osteogenic differentiation of BMSCs by increasing the expression of SIRT1. The increased expression of SIRT1 significantly reduced BMSC apoptosis during osteogenic differentiation, which is one of the important mechanisms by which SIRT1 regulates the osteogenic ability of BMSCs. Our data also provide strong evidence that resveratrol may be used in the treatment of osteoporosis in patients with T2DM.
2 型糖尿病(T2DM)患者存在发生骨质疏松症的高风险。SIRT1 在糖尿病的发生和发展中发挥重要的调节作用;然而,SIRT1 是否与 T2DM 患者骨髓间充质干细胞(BMSCs)的成骨能力直接相关仍不清楚。
我们从 T2DM 患者和健康志愿者中获取 BMSCs,以确定 SIRT1 表达对 BMSCs 成骨能力的影响。结果表明,T2DM 患者 BMSCs 中的 SIRT1 表达明显低于健康志愿者,但 T2DM 组 BMSCs 的增殖能力与健康志愿者无显著差异。
在成骨分化过程中,T2DM 患者的 MSC 中 SIRT1 的表达明显降低,T2DM 患者的 MSC 成骨分化能力明显低于健康志愿者。用白藜芦醇干预后,SIRT1 的表达明显增加,T2DM 患者的 MSC 凋亡率明显降低。此外,白藜芦醇促进了 MSC 的成骨分化。
我们的研究证实,SIRT1 的表达与 T2DM 患者 BMSCs 的成骨潜能直接相关。白藜芦醇通过增加 SIRT1 的表达促进了 BMSCs 的成骨分化。SIRT1 表达增加显著减少了成骨分化过程中 BMSC 的凋亡,这是 SIRT1 调节 BMSCs 成骨能力的重要机制之一。我们的数据还为白藜芦醇可能用于治疗 T2DM 患者的骨质疏松症提供了有力证据。