Background

Inflammation is one of major contributors of diabetic osteoporosis. Here, we combined adipose tissues derived mesenchymal stem cells (AD-MSCs)-derived exosomes and microRNA-146a (miR-146a) to develop more effective anti-inflammation strategy in osteoclasts.

Methods

miR-146a was overexpressed in AD-MSCs and miR-146a exosomes (miR-146a-Exo) were isolated and characterized. Cellular and animal diabetic osteoporosis models were created to evaluate the anti-inflammation effect of miR-146a-Exo by using ELISA, qRT-PCR, MTT, bone resorption assay, Western blot, and bone mineral content and density analysis in vitro and in vivo.

Results

miR-146a-Exo administration presented the most potent effect on inhibition of pro-inflammatory cytokines production in high glucose-treated osteoclasts, restraint bone resorption, and restoration of the bone loss in streptozotocin-induced diabetic osteoporosis rats. Mechanistically, miR-146a-Exo suppressed the expression of TNF-α, IL-18, and IL-1β, induced the inactivation of inflammasome, and finally reduced bone resorption and recovered bone loss.

Conclusion

Combination of AD-MSCs-Exo and miR-146a more effectively exert the anti-inflammation effect in osteoclasts, providing a potential drug for the treatment of diabetic osteoporosis.

中文翻译：

---

来自过度表达 MicroRNA-146a 的间充质干细胞的脂肪组织外泌体减轻大鼠糖尿病性骨质疏松症

背景

炎症是糖尿病性骨质疏松症的主要诱因之一。在这里，我们将脂肪组织衍生的间充质干细胞 (AD-MSCs) 衍生的外泌体和 microRNA-146a (miR-146a) 结合起来，以开发更有效的破骨细胞抗炎策略。

方法

miR-146a 在 AD-MSCs 中过表达，分离并表征了 miR-146a 外泌体（miR-146a-Exo）。建立细胞和动物糖尿病骨质疏松模型，通过使用 ELISA、qRT-PCR、MTT、骨吸收测定、蛋白质印迹以及体外和体内骨矿物质含量和密度分析来评估 miR-146a-Exo 的抗炎作用.

结果

miR-146a-Exo 给药对抑制高葡萄糖处理的破骨细胞中促炎细胞因子的产生、抑制骨吸收和恢复链脲佐菌素诱导的糖尿病性骨质疏松大鼠的骨丢失具有最有效的作用。机制上，miR-146a-Exo 抑制 TNF-α、IL-18 和 IL-1β 的表达，诱导炎性体失活，最终减少骨吸收并恢复骨丢失。

结论

AD-MSCs-Exo与miR-146a联合使用更有效地发挥破骨细胞的抗炎作用，为治疗糖尿病性骨质疏松症提供了潜在的药物。