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骨髓间充质干细胞移植对去卵巢骨质疏松大鼠骨密度的影响
Bone marrow mesenchymal stem cell transplantation increases bone mineral density of an ovariectomized rat model of osteoporosis
【摘要】 背景:骨髓间质干细胞可向成骨细胞分化,移植后可向病变部位迁移等特性,使其在骨质疏松中的研究受到越来越多的关注和重视。目的:观察骨髓间质干细胞移植对去卵巢骨质疏松大鼠骨密度的影响及其可能的作用机制。方法:(1)采用全骨髓贴壁培养法,从幼年SD大鼠股骨和胫骨骨髓中分离培养骨髓间质干细胞;(2)将成年雌性大鼠30只随机分为3组:假手术组、卵巢切除组、卵巢切除+骨髓间质干细胞移植组,每组10只。待骨质疏松模型建立成功后,卵巢切除+骨髓间质干细胞移植组大鼠经尾静脉注射含3.5×109 L-1骨髓间质干细胞的PBS溶液(80μL/kg),其他2组注射等量的PBS溶液;(3)细胞移植第2周,采用双能X射线骨密度仪测量各组大鼠股骨骨密度、腰椎骨密度及全身骨密度,并测定血清钙、磷、碱性磷酸酶及骨钙素水平,micro-CT扫描进行胫骨组织微结构形态计量学分析。结果与结论:(1)卵巢切除组大鼠股骨骨密度、腰椎骨密度及全身骨密度显著低于假手术组;卵巢切除组大鼠血清中钙、骨钙素水平也显著低于假手术组,而磷、碱性磷酸酶水平明显升高,差异有显著性意义(P<0.05或P<0.01),以上表明骨质疏松大鼠模型成功制备;(2)与卵巢切除组大鼠相比,卵巢切除+骨髓间质干细胞移植组大鼠股骨、腰椎及全身骨密度均明显增加,血清中钙、骨钙素水平亦显著升高,而血清磷、碱性磷酸酶水平下降,差异均有显著性意义(P<0.05);(3)与卵巢切除组比较,卵巢切除+骨髓间质干细胞移植组大鼠的骨体积分数、骨小梁数量和骨小梁厚度均显著增加,差异有显著性意义(P<0.05);(4)结果表明,骨髓间质干细胞移植能够提高卵巢切除骨质疏松大鼠骨密度,促进骨形成。
【Abstract】 BACKGROUND: Bone marrow mesenchymal stem cells(BMSCs) can be differentiated into osteoblasts, and migrate to lesion sites after transplantation, which have attracted more and more attentions in the research of osteoporosis. OBJECTIVE: To study the effect of BMSCs transplantation on bone mineral density in an ovariectomized rat model of osteoporosis and its possible mechanism of action. METHODS: Using the whole bone marrow culture method, BMSCs were isolated from the femur and tibia of juvenile Sprague-Dawley rats. Thirty adult female rats were randomly divided into three groups: control group, ovariectomized group, and cell transplantation group, with 10 rats in each group. Osteoporosis models were made in ovariectomized and cell transplantation group. Then, PBS solution containing 3.5×10~9/L BMSCs at a dose of 80 μL/kg was injected via the tail vein into the rats in the cell transplantation group, while the same volume of PBS solution was injected in the other two groups. Two weeks later, dual-energy X-ray absorptiometry was used to measure bone mineral density of the femur, lumbar spine and whole body. Serum levels of calcium, phosphorus, alkaline phosphatase and osteocalcin were determined. Micro-CT was used for morphometric analysis of the tibial microstructure. RESULTS AND CONCLUSION: After ovariectomy, there was a significant reduction in the bone mineral density of the rat femur, lumbar spine and whole body as well as the levels of serum calcium and osteocalcin; however, the phosphorus and alkaline phosphatase levels were increased significantly(P < 0.05 or P < 0.01). These findings indicate the successful preparation of the osteoporosis rat model. Compared with the ovariectomized group, the bone mineral density of the rat femur, lumbar spine or whole body was significantly higher in the cell transplantation group, and significantly increased serum calcium and osteocalcin and significantly decreased phosphorus and alkaline phosphatase levels were also found in the cell transplantation group(P < 0.05). Additionally, the bone volume fraction, number of trabeculae and thickness of trabecular bone were significantly increased in the cell transplantation group compared with the ovariectomized group(P < 0.05). To conclude, our results show that BMSCs can improve the bone mineral density of osteoporosis rats induced by ovariotomy, and thereby promote new bone formation.
【Key words】 ,Osteoporosis, Postmenopausal; Bone Marrow; Mesenchymal Stem Cell Transplantation; Bone Density; Tissue Engineering;
- 【文献出处】 中国组织工程研究 ,Chinese Journal of Tissue Engineering Research , 编辑部邮箱 ,2017年01期
- 【分类号】R580
- 【被引频次】19
- 【下载频次】314