淫羊藿苷-PLGA骨靶向缓释微球介导自噬逆转BMSC衰老防治老龄化骨质疏松的研究

With the acceleration of aging in China, the incidence of fractures caused by osteoporosis continues to rise, which seriously affecting the quality of life of the aged and even life-threatening. However, due to the weak bone regeneration ability, complicated condition, and poor surgical tolerance of the elderly patients, the adoption of existing materials and conventional methods to treat osteoporotic fractures is often unsatisfied. Therefore, it is urgent to find new techniques and/or strategies to strengthen the bone density of aging bone tissue prior to the occurrence of the osteoporotic fracture, so as to greatly reduce the incidence of fractures. Accordingly, the present study proposes to rejuvenate the senescence of bone marrow mesenchymal stem cells (BMSCs), that is, maintaining their stemness and activity of osteogenic differentiation through icariin-mediated autophagy, aiming to improve the bone density of the aging bone. Firstly, controlled release icariin PLGA microspheres are prepared intends to regulate the autophagy of aging BMSCs, the underlying molecular mechanism is also elucidated; Then investigating the in vitro functional rejuvenation of aging BMSCs by icariin-mediated autophagy, that is, the stemness and activity of osteogenic/adipogenic differentiation. Meanwhile, exploring the effects of microenvironment manipulated by aging BMSCs on osteoblasts/osteoclasts function and its underlying molecular mechanisms after autophagy activation; Finally, verifying the in vivo effect of icariin on the prevention of osteoporosis. This study can strengthen the bone density of the aged by rejuvenating the aging of BMSCs from the perspective of autophagy, which can not only perfect the current knowledge of icariin in preventing and treating osteoporosis, but also provide therapeutic target and reference basis for the prevention and treatment of osteoporosis and the development of therapeutic drugs.

随着我国老龄化社会的加速到来，因骨质疏松造成的骨折发病率持续上升，其致残率和致死率极高，严重影响老年人的生活质量。当下迫切需要在骨质疏松性骨折发生前寻找新策略强化老龄化骨组织骨质密度，防患于未然，从而大幅降低骨折发生率。本课题提出通过淫羊藿苷介导自噬逆转骨髓间充质干细胞（BMSCs）衰老即维持其干性和成骨分化能力以解决该问题。通过制备淫羊藿苷-PLGA骨靶向缓释纳米微球，介导PLGA微球的降解调控淫羊藿苷在骨组织靶向缓释，进而激活衰老BMSCs自噬；其后重点考察淫羊藿苷介导的自噬对衰老BMSCs功能逆转的影响及其营造的微环境对成骨/破骨细胞功能的影响；最后通过体内实验验证淫羊藿苷对骨质疏松的防治效果。本课题从自噬角度出发，通过逆转BMSCs衰老提升老龄患者骨质密度，不仅可以完善淫羊藿苷防治骨质疏松的潜在机理，同时有望为骨质疏松的防治和治疗药物的研发提供新靶点和参考依据。

随着我国老龄化社会的加速到来，因骨质疏松造成的骨折发病率持续上升，其致残率和致死率极高，严重影响老年人的生活质量。当下迫切需要在骨质疏松性骨折发生前寻找新策略强化老龄化骨组织骨质密度，防患于未然，从而大幅降低骨折发生率。本课题提出通过淫羊藿苷介导自噬逆转骨髓间充质干细胞（BMSCs）衰老即维持其干性和成骨分化能力以解决该问题。通过制备淫羊藿苷-PLGA骨靶向缓释微球，介导PLGA的降解调控淫羊藿苷在骨组织靶向缓释，进而激活衰老BMSCs自噬；其后重点考察淫羊藿苷介导的自噬对衰老BMSCs功能逆转的影响及其营造的微环境对成骨/破骨细胞功能的影响；最后通过体内实验验证淫羊藿苷对骨质疏松的防治效果。本课题从自噬角度出发，借助材料生物学效应，通过逆转BMSCs衰老提升老龄患者骨质密度，不仅完善了淫羊藿苷防治骨质疏松的潜在机理，同时为骨质疏松的防治和治疗药物的研发提供了新靶点和参考依据。