Accompanying with diabetes mellitus‐induced osteoporosis (DM‐OS), diabetic patients show poor peri‐implant osteogenesis after implantation for dentition defect. Berberine (BBR), a candidate oral hypoglycemic agent, is a promising agent for treating DM‐OS. In this study, BBR was applied on DM rats and high‐glucose‐cultured bone mesenchymal stem cells (BMSCs) to investigate its therapeutic mechanism on DM‐OS, thus laying a theoretical basis for the future application of BBR in implant restoration. Phenotypes were assessed in the DM rats after 4 w of gavage with BBR. Furthermore, BMSCs were cultured with high glucose and BBR. Cell Counting Kit‐8, 2′,7′‐dichlorofluorescin diacetate (H₂DCF‐DA), quantitative real‐time PCR (qRT‐PCR), and western blot were performed to estimate the cell proliferation, oxidative stress, and osteogenic differentiation. Moreover, the DM rats treated with BBR and insulin receptor substrate‐1 anti‐sense oligonucleotide (IRS‐1‐ASO) underwent a 4‐w implant‐healing period and then micro computed tomography (Micro‐CT) and histology were performed to verify the mechanism. Results showed that the 4‐w administration of BBR markedly improved the glucose metabolism and bone metabolism in the DM rats. in vitro experiments revealed that BBR alleviated high‐glucose‐inhibited osteogenesis of the BMSCs by upregulating reactive oxygen species (ROS)‐mediated IRS‐1 signaling. Besides, injection of IRS‐1‐ASO abolished the BBR promotion of implant osseointegration in the DM rats. In conclusion, targeting ROS‐mediated IRS‐1 signaling, BBR acted as an efficient agent to advance osseointegration in DM, which indicated that BBR use is a good strategy for future implants restoration in diabetic patients.

中文翻译：

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小檗碱通过ROS介导的IRS-1途径促进糖尿病大鼠种植体周围成骨


伴随着糖尿病引起的骨质疏松症（DM-OS），糖尿病患者在牙列缺损种植后表现出种植体周围成骨不良。小檗碱 (BBR) 是一种候选口服降血糖药，是治疗 DM-OS 的有前途的药物。本研究将BBR应用于DM大鼠和高糖培养的骨间充质干细胞（BMSCs），探讨其对DM-OS的治疗机制，为未来BBR在种植体修复中的应用奠定理论基础。用 BBR 灌胃 4 周后，对 DM 大鼠的表型进行评估。此外，BMSCs用高葡萄糖和BBR培养。使用细胞计数试剂盒-8、2',7'-二氯荧光素二乙酸酯 (H ₂ DCF-DA)、实时定量 PCR (qRT-PCR) 和蛋白质印迹来评估细胞增殖、氧化应激和成骨分化。此外，用BBR和胰岛素受体底物-1反义寡核苷酸（IRS-1-ASO）治疗的DM大鼠经历了4周的植入愈合期，然后进行显微计算机断层扫描（Micro-CT）和组织学检查以验证的机制。结果显示，BBR 4周给药显着改善DM大鼠的糖代谢和骨代谢。体外实验表明，BBR 通过上调活性氧 (ROS) 介导的 IRS-1 信号传导来减轻高葡萄糖抑制的 BMSC 成骨作用。此外，注射 IRS-1-ASO 消除了 BBR 对 DM 大鼠种植体骨整合的促进作用。总之，针对 ROS 介导的 IRS-1 信号传导，BBR 是促进 DM 骨整合的有效药物，这表明 BBR 的使用是糖尿病患者未来种植体修复的良好策略。