供体MSCs来源的外泌体转运miR-26a恢复宿主MSCs功能并缓解骨质疏松

Rescue of recipient MSC functions and remission of recipient osteoporosis by donor MSC-derived exosomes through transfer of miR-26a

目的:探讨移植的供体间充质干细胞(mesenchymal stem cells,MSCs)通过分泌外泌体缓解雌激素缺乏导致的骨质疏松的机制。方法:建立12只小鼠雌激素缺乏骨质疏松模型,通过siRNA调控MSCs外泌体释放及直接注射外泌体,明确外泌体的分泌在MSCs治疗骨质疏松中的作用;通过体外成骨分化诱导、茜素红染色、qPCR明确供体MSCs来源的外泌体对宿主MSCs功能的影响;通过miR-26a模拟物、抑制物转染、qPCR明确外泌体发挥治疗作用的机制。结果:供体MSCs通过分泌外泌体缓解雌激素缺乏骨质疏松,并证明外泌体通过恢复骨质疏松宿主MSCs成骨分化功能缓解骨质疏松,外泌体可通过转运miR-26a恢复骨质疏松宿主MSCs的成骨分化功能。结论:供体MSCs来源的外泌体可通过转运miR-26a恢复宿主MSCs功能并缓解骨质疏松。

Objective： To explore mechanisms underlying the rescuing effects of transplanted mesenchymal stem cells （MSCs） derived exosomes on estrogen-deficient osteoporosis. Methods： Mouse estrogen-deficient osteoporosis model was constructed in 12 female C57BL6/J rats and the exosome release was regulated by siRNA. Osteogenic induction, alizarin red staining and qPCR were performed to evaluate the effects of exosomes on recipient MSC functions. The miR-26a mimics and inhibitors and qPCR were used to explore the mechanisms underlying exosome-mediated functional rescue of recipient MSCs. Results： Donor MSCs alleviated estrogen-deficient osteoporosis via exosome release, and the alleviated osteoporosis by exosomes rescued the recipient MSC functions were observed. Moreover, the rescued recipient MSC functions by exosomes transferred miR-26a were found. Conclusion： Donor MSC-derived exosomes may rescue MSC functions and may remit osteoporosis of the recipient through transfering miR-26a.