VD/VDR调控FGF23-Klotho轴在衰老骨髓间充质干细胞成骨分化中的作用及黄芪干预机制

Primary osteoporosis is a serious common and frequently occurring disease that threat to the elderly health.The osteoblast differentiation abnormal of bone marrow mesenchymal stem cells is one of the important mechanisms of primary osteoporosis.Regulation aging bone marrow mesenchymal stem cells to osteoblast differentiation is an important means to prevention and cure for primary osteoporosis. Present study shows that vitamin D/VDR regulate FGF23-Klotho axis can be used as important targets for treatment osteoporosis through the osteogenetic differentiation from aging mesenchymal stem cells.The early stage of the research literature and experimental discovery that Astragalus Membranaceus can adjust serum vitamin D, FGF23, Klotho in osteoporosis rats model and improve pathological processes. Our team hypothesis that Astragalus Membranaceus act on vitamin D/VDR then regulate FGF23-Klotho axis to improve the osteogenetic differentiation of aging mesenchymal stem cells.Using cytobiology siRNA technology to explore the molecular mechanism of Astragalus Membranaceus intervention osteogenetic differentiation of aging mesenchymal stem cells through the vitamin D/VDR regulate FGF23 -Klotho axis.And combined with the natural fast ageing mice SAMP6 as experimental model to observe the effect on osteoporosis through improve osteogenetic differentiation of aging mesenchymal stem cells by astragalus membranaceus intervention. To provide a new research idea for prevention and treatment of primary osteoporosis of traditional Chinese medicine.

原发性骨质疏松症是严重威胁老年人健康的常见疾病。原发性骨质疏松症的重要机制之一是骨髓间充质干细胞（BMSCs）成骨分化异常，调控衰老BMSCs成骨分化是原发性骨质疏松症防治的重要手段。维生素D/VDR调控FGF23-Klotho轴是改善衰老BMSCs成骨分化的重要途径，是治疗原发性骨质疏松症的靶点。实验发现，黄芪能调节骨质疏松大鼠模型血清维生素D、FGF23、Klotho，改善骨质疏松大鼠模型病理进程。由此提出黄芪通过维生素D/VDR调控FGF23-Klotho轴，改善衰老BMSCs活力和骨形成的分子机制假说。拟运用细胞生物学siRNA技术，探讨黄芪通过维生素D/VDR调控FGF23-Klotho轴干预衰老BMSCs成骨分化的分子机制，结合自然快速老化模型SAMP6小鼠为实验对象，从整体水平探讨黄芪干预BMSCs衰老进程改善小鼠骨质疏松症效应，为中医药防治原发性骨质疏松症提供新的研究思路。

骨质疏松症（Osteoporosis，OP）是一种骨代谢紊乱引发的进展性骨骼系统疾病，可累及全身骨骼，以骨量丢失、骨密度降低、骨微结构退化或破坏、骨脆性及骨折率增高等为特点。我国大陆地区40岁以上患有骨质疏松症的人群达到约1.1亿，且该病骨折危害大，致残率及病死率高。原发性骨质疏松症的重要机制之一是骨髓间充质干细胞（BMSCs）成骨分化异常，调控衰老BMSCs成骨分化是原发性骨质疏松症防治的重要手段。维生素D（VitaminD, VD）是机体内调节骨无机盐代谢的重要物质基础，既可以促进新骨钙化，又可促进钙从骨中游离出来，使骨盐不断更新，以维持钙的平衡。目前，临床上治疗骨质疏松症基本药物主要为钙剂和维生素D补充剂。维生素D受体（VDR）是介导维生素D发挥其生物效应的一种亲核蛋白，与维生素D共同构成维生素D轴（VD/VDR或维生素D系统）。除维生素D、VDR外，维生素D轴还包括25-羟基维生素D3-1α-羟化酶（CYP27B1）、维生素D3-24-羟化酶（CYP24A1）等基因与蛋白。由此本项目实验运用细胞生物学siRNA技术，探讨黄芪通过维生素D/VDR调控FGF23-Klotho轴干预衰老BMSCs成骨分化的分子机制，结合自然快速老化模型SAMP6小鼠为实验对象，从整体水平探讨黄芪干预BMSCs衰老进程改善小鼠骨质疏松症效应，为中医药防治原发性骨质疏松症提供新的研究思路。