低强度力学刺激调控骨髓间充质干细胞定向分化和破骨细胞分化促进骨质疏松大鼠骨形成机理研究

项目名称： 低强度力学刺激调控骨髓间充质干细胞定向分化和破骨细胞分化促进骨质疏松大鼠骨形成机理研究

项目编号： No.11272225

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 李良

作者单位： 四川大学

项目金额： 106万元

中文摘要： 骨质疏松症（osteoporosis）是一种最常见与年龄相关的全身性骨骼系统疾病，其所导致的骨折已成为世界公共卫生难题。控制这种疾病仍然非常困难。低强度全身振动已成为骨质疏松治疗的备选方案之一。但力学刺激如何促进骨形成的机理仍不清楚。因此，本研究假设骨质疏松症是由于成骨细胞的起源，及骨髓间充质干细胞出现增龄性退化，导致成骨细胞形成不足，进而导致破骨细胞分化异常，致使骨丢失。从动物模型到细胞分子水平，系统地研究低强度全身振动所产生的力学刺激促进绝经后骨质疏松和老年骨质疏松大鼠模型骨形成机制，以及这两种骨质疏松模型骨形成机理的异同；探讨力学刺激调控骨质疏松大鼠MSCs定向分化能力、以及破骨细胞分化能力的可能的信号途径，期望为骨质疏松症的预防和治疗提供一个非药理学的、有效的、无创性的、易于接受且可以长期坚持的治疗选项。

中文关键词： 骨髓间充质干细胞；力学刺激；骨质疏松；低强度全身振动；骨生成

英文摘要： Osteoporosis, a disease characterized by diminished bone density, is one of the most prevalent and serious age-related disorders， with atraumatic fractures severely compromising an individual's quality of life. Osteoporosis constitutes a major public health problem and the treatment and prevention of osteoporosis involve great challenges. One proposed alternative is low-magnitude whole-body vibration therapy, which may be safer than drugs and may increase bone mineral density (BMD). But it is unknown how the mechanism of the mechanical stimulation by the therapy improve BMD. We hypothesis that the ability of self-renew and differentiation in bone marrow mesenchymal stem cells (BMSCs) were decreased with aging and the bias of BMSCs lineage selection shift adipocyte formation. Number of osteoblast and pre-osteoblast were decrease because bone marrow osteoprogenitors are inversely proportional to adipocyte precursors. However, OPG/RANKL secreted by Osteoblast and pre-osteoblast were closely related to regulation of osteoclast differentiation. So, the aim of the project to investigate whether the low -magnitude mechanical stimulation increase bone formation in rat osteoprotic model by regulating the biasing of BMSCs differentiation and osteoclast differentiation.

英文关键词： rat bone marrow-derived mesenchymal stem cells；mechanical stimulation；osteoporosis；low-intensity whole body vibration；osteogenesis;