运动对废用性骨质疏松大鼠破骨细胞分化JNK/AP-1信号通路的影响

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目的通过尾部悬吊的方法制造大鼠废用性骨质疏松模型,从破骨细胞分化及其JNK/AP-1信号通路的角度研究跑台运动对废用性骨质疏松的康复作用,以期从细胞及分子层面揭示其内在机制。方法 6周龄雄性Sprague-Dawley大鼠40只,分为正常对照组、废用模型组、正常恢复组和运动恢复组,每组10只。各组大鼠经过不同的干预方案后处死,其中正常对照组不做任何特殊处理,安静饲养4周后处死;废用模型组尾部悬吊4周后处死;正常恢复组尾部悬吊4周后,安静饲养4周处死;运动恢复组尾部悬吊4周后,跑台训练4周处死。各组大鼠处死后立即进行骨密度测试,同时对骨髓造血干细胞进行培养,诱导其向破骨细胞分化,通过对破骨细胞特异性酶——抗酒石酸酸性磷酸酶(TRACP-5b)的染色以检测破骨细胞的生成情况,通过Western blot方法检测破骨细胞分化JNK/AP-1信号通路相关蛋白的表达。结果与正常对照组相比,废用模型组大鼠骨密度显著下降,破骨细胞生成显著增加,破骨细胞分化JNK/AP-1信号通路相关蛋白表达显著增加;与正常恢复组相比,运动恢复组大鼠骨密度显著升高,破骨细胞生成显著降低,破骨细胞分化JNK/AP-1信号通路相关蛋白表达显著降低。结论 4周的尾部悬吊可显著增加大鼠破骨细胞的分化、降低大鼠的骨密度,跑台运动可以有效抑制尾部悬吊大鼠破骨细胞的分化和骨密度的下降;尾部悬吊及跑台运动对大鼠破骨细胞分化的影响与JNK/AP-1信号通路相关蛋白的表达密切相关。 OBJECTIVE: To establish a rat model of disuse osteoporosis by caudal suspension and to study the rehabilitation effect of treadmill exercise on disuse osteoporosis in terms of osteoclast differentiation and JNK / AP-1 signaling pathway. From the cellular and molecular level revealed its internal mechanism. Methods Forty male Sprague-Dawley rats aged 6 weeks were divided into normal control group, untreated group, normal recovery group and exercise recovery group, 10 rats in each group. The rats in each group were sacrificed after different interventions. The rats in the normal control group were sacrificed after 4 weeks and were sacrificed after 4 weeks of caudal suspension. The rats in the normal recovery group were suspended for 4 weeks Were sacrificed for 4 weeks and sacrificed for 4 weeks. After tail suspension for 4 weeks, treadmill training was executed for 4 weeks. The bone mineral density (BMD) of the rats in each group was measured immediately after the sacrifice, and the bone marrow hematopoietic stem cells were cultured to induce their differentiation into osteoclasts. The osteoclast-specific tacrolimus acid phosphatase (TRACP-5b) To detect the formation of osteoclasts, Western blot was used to detect the expression of JNK / AP-1 signaling pathway-related proteins in osteoclasts. Results Compared with the normal control group, the bone mineral density of the untreated group was significantly decreased, the osteoclast formation was significantly increased, and the expression of JNK / AP-1 signaling pathway-related protein was significantly increased in osteoclasts compared with the normal control group. Compared with the normal recovery group, The bone mineral density of rats in exercise rehabilitation group was significantly increased, osteoclast formation was significantly reduced, and the expression of JNK / AP-1 signaling pathway-related proteins in osteoclasts was significantly decreased. Conclusion Tail suspension at 4 weeks can significantly increase osteoclast differentiation and decrease bone mineral density in rats. Treadmill exercise can effectively inhibit osteoclast differentiation and decrease bone mineral density in tail suspension rats. Tail suspension And treadmill exercise on osteoclast differentiation of rat are closely related to the expression of JNK / AP-1 signaling pathway related proteins.
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