项目名称: 异基因MSC抑制TNF-α促进成骨分化治疗类风湿关节炎骨质疏松的机制研究
项目编号: No.81202350
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学免疫学、法医学
项目作者: 张华勇
作者单位: 南京大学
项目金额: 24万元
中文摘要: 类风湿关节炎(RA)继发骨质疏松是RA骨破坏的主要因素之一,既往认为TNF-α等炎症因子诱导破骨细胞生成增多是RA骨质疏松发生的关键因素,但TNF-α对成骨细胞作用的研究目前较少。骨髓间充质干细胞(MSC)具有向成骨细胞分化的功能,而我们前期研究发现RA患者TNF-α水平增高,且抑制骨髓MSC成骨分化能力,可能参与RA骨质疏松发生;异基因MSC移植能改善难治性RA患者病情,降低TNF-α水平,更重要的是部分RA骨质疏松患者骨密度得到改善。因此,我们推测异基因MSC移植可能通过降低RA患者TNF-α水平、提高骨髓MSC的成骨分化能力从而改善RA骨质疏松。在前期实验基础上,本课题将进一步研究TNF-α抑制RA患者MSC成骨分化的机制,探讨异基因MSC移植降低TNF-α水平对MSC成骨能力的影响以及与骨质疏松的关系。研究结果将为MSC临床治疗RA骨质疏松提供新的靶点及理论依据。
中文关键词: 类风湿关节炎;间充质干细胞;成骨细胞;破骨细胞;骨质疏松
英文摘要: The secondary osteoporosis is the principal reason of bone structural deterioration in patients with rheumatoid arthritis (RA). Increased level of TNF-α gives rise to a high turnover rate in bone metabolism, as characterized by an over-activated osteoclast activity. However, the effect of TNF-α on osteoblasts is poorly studied. In our previous study, we have proved that allogeneic mesenchymal stem cells (MSC) transplantation is a novel therapeutic option for refractory RA, and we have observed that MSC transplantation could reduce the level of TNF-α and increase the bone mineral density of patients with osteoporosis, but the mechanism is not clear. Here we speculated that allogeneic MSC transplantation could promote osteoblastic differentiation in treating osteoporosis of RA through inhibiting the level of TNF-α, which was elevated in RA patients. In the current study, we will further observe the critical role of TNF-α in the osteoblasts regulation by MSC in vivo and in vitro, thereby to deeply indicate the mechanisms by which allogeneic MSC modulate osteoblast and treat RA osteoporosis.
英文关键词: Rheumatoid arthritis;Mesenchymal stem cells;Osteoblast;Osteoclast;Osteoporosis