骨髓间充质干细胞在小鼠早衰性骨质疏松中的细胞生物学功能研究

 目的：研究在小鼠早衰性骨质疏松症中骨髓间充质干细胞（BMMSCs）功能的变化，为揭示骨质疏松发病机制提供理论依据。方法：以早衰小鼠（SAMP6）为动物模型（对照小鼠：SAMR1），分离培养3个月与6个月小鼠的BMMSCs，利用流式细胞术进行干细胞表型鉴定后用于基因芯片检测筛选差异表达基因，并对该结果进行了Pathway分析。分离培养鉴定2组的BMMSCs并对其成骨与成脂的分化能力进行比较，在诱导分化后进行实时定量RT-PCR检测相关基因的表达，揭示骨髓间充干细胞功能在早衰性骨质疏松中的改变。结果：本研究证明了随着年龄的增长，骨髓间充质干细胞成骨能力降低而成脂能力增高；芯片结果的Pathway分析显示，转化生长因子β（TGF-β）信号通路有4个关键基因发生改变，提示TGF-β信号通路可能在此过程中发挥重要作用。结论：随着年龄增长，早衰性骨质疏松个体的骨髓间充质干细胞生物学功能及TGF-β通路发生了改变，为通过改变骨髓间充质干细胞的生物学功能从而有效逆转治疗、改善骨质疏松状态提供靶点和理论依据。

Age-related changes of bone marrow mesenchymal stem cells in senile osteoporosis

AIM：To investigate the different functions of bone marrow mesenchymal stem cells (BMMSCs) in age-related osteoporosis. METHODS：The senescence-accelerated mice (SAMP6) were used in the experiment. The BMMSCs were isolated from femora and tibiae by flushing. Flow cytometric analysis was performed with MSCs-related monoclonal antibodies. The expression of differentiation genes was tested by real-time RT-PCR. RESULTS：In the progress of age-related osteoporosis, BMMSCs exhibited a decrease in osteogenesis and an increase in adipogenesis. Transforming growth factor β(TGF-β) signaling was significantly changed along with aging in SAMP6 mice. CONCLUSION：The functional changes of BMMSCs may play an important role in senile osteoporosis. The alteration of TGF-β-related gene expression may be the molecular mechanism of dysfunction in BMMSCs.