淫羊藿苷上调BMP-Smad通路防治绝经后骨质疏松症

Postmenopasusal osteoporosis is a serious public health issue and one of the most important aging-associated diseases, affecting millions of people. Postmenopasusal osteoporosis always treated by estrogen, but the outcome of studies aiming at the investigation of estrogenic effects of compounds potentially used in hormone replacement is pessimistic, which known as many sideeffect. For postmenopausal women, Epimedium pubescens favonoids exert a benefcial effect on preventing bone loss, icariin, one of the primary active ingredients of Epimedium, reportedly has a potential anabolic effect on the bone. Our preliminary work showed that icariin possibly exerted its osteogenic effects through the induction of BMP-2 gene expression. Many findings demonstrated that Smads are intracellular signaling proteins that transduce signals elicited by members of BMP signaling in osteoblasts. We, therefore, in this study investigated whether icariin could treat postmenopasusal osteoporosis in vivo and in vitro. A postmenopausal osteoporosis model was generated in oophorectomized (OVX) osteopenic rats, investigated whether icariin could induce BMP-Smad signaling pathway changes of MC3T3-E1 cells. We will detect the expression of serum calcium, phosphorus, osteocalcin, bone density, bone formation and osteoclast activity, endocrine, bone cell ultrastructure and BMP-Smad signaling pathway related genes. At last, Noggin (BMP inhibitor) will be add in MC3T3-E1 cells to infirm the potentially molecular mechanism of the osteogenic effects of icariin. Our observations will suggest that icariin facilitates osteoblast proliferation and differentiation possibly through the BMP- Smad signaling pathway.

绝经后骨质疏松症(PMOP)是一种严重威胁中老年妇女健康的常见病，目前还没有一种安全、有效的根治办法。雌激素替代治疗是常用方法，但雌激素作用靶点多，长期使用会带来许多副作用和不良反应。淫羊藿苷是淫羊藿的主要成分之一，在前期工作中我们发现淫羊藿苷可上调MC3T3-E1细胞BMP-2的表达。已知，BMP-Smad信号通路的异常会造成骨相关疾病，本课题拟采用大鼠去势模型与成骨细胞MC3T3-E1观察其防治作用，并进一步探索BMP-Smad信号通路在淫羊藿苷预防PMOP中的作用机制。我们通过在体和离体两个层面，检测干预前后血清钙、磷、骨钙素、骨密度、成骨及破骨细胞活性、内分泌、骨细胞超微结构及BMP-Smad信号通路相关基因的表达，最后通过BMP抑制剂Noggin反证其有效性，为临床应用提供实验依据，为PMOP的药物治疗提供一种新的策略。

绝经后骨质疏松症(PMOP)是一种严重威胁中老年妇女健康的临床常见病、多发病，近年由于生活质量的提高，越来越受到临床医师及科研工作者的关注，但本病目前尚缺乏疗效好、副作用小的治疗方法。现代研究表明淫羊藿的抗骨质疏松疗效可靠，有开发前景，本实验选取淫羊藿苷，针对单一药物成分进行研究，可以排除因中药组方中药物及成分繁多而无法确定其具体起效成分的弊端。本实验运用大鼠去势骨质疏松模型与成骨细胞MC3T3-E1体外培养模型观察淫羊藿苷对PMOP的预防作用，并进一步探索其作用机制，为PMOP的治疗开辟了一条新的思路。我们通过在体和离体两个层面，检测干预前后血清钙、骨钙素、骨密度值、ALP活性、细胞增殖及BMP-Smad信号通路相关基因的表达，评估淫羊藿苷治疗PMOP的有效性，为其临床应用提供实验依据，为PMOP的药物治疗提供一种新选择，为PMOP的中医药治疗提供新策略。通过研究，我们发现，淫羊藿苷对MC3T3⁃E1前体成骨细胞的形态无明显影响，淫羊藿苷可能通过上调细胞BMP⁃2蛋白的表达，激活BMP⁃2/Smads信号通路，启动下游成骨相关基因的表达，从而促进MC3T3⁃E1细胞的增殖、分化。本研究首次探讨BMP-Smad信号通路在淫羊藿苷预防PMOP中的作用及其机制，目前这些思路在国内外显见报道。