旋转恒定磁场对炎性诱发增龄型骨衰老疾病的疗效及分子机制

Bone degeneration is an early syndrome of aging diseases, the symptom complex will be recovered after magnetic field exposure, however, the molecular mechanism remain unclear. This research plan is to investigate the molecular markers and rehabilitation effects of rotary magnetic fields (RMFs) exposure on bone aging diseases. Specifically, we have created bone aging mouse model using SHP2-conditional knockout mice. The mice will be used in four subaims. (1) The limb function and activities, spine deformation, bone aging disorder and inflammation in bone aging mice with or without magnetic field exposure will be examined. (2) The changes of protein and small molecule metabolites in serum of bone aging mice with or without magnetic field exposure were examined by serum proteomics and metabolomics. (3) The transcriptional profile of T cells and bone cells in bone aging mice with or without magnetic field exposure will be determined by deep sequencing technology. (4) The molecular diagnostic markers of bone aging related diseases such as osteoporosis and bone hyperplasia will be identified. These four aims will unreveal the molecular events associated with pathogenesis of bone aging related diseases after magnetic field treatment, which will be the basis for therapy evaluation and screening for bone aging related diseases treatment.

骨衰老是人体衰老早发症状之一，可谓“看老先看腿”，增龄型骨关节疾病与长期慢性炎症刺激相关，目前骨衰老发生机制不明，尚无药可医。本研究团队多年研究表明磁场能有效缓解激素源性的骨质疏松及激素源性股骨头坏死等骨关节疾病，而对增龄型骨关节疾病的康复疗效及作用靶点尚未知。本项目采用T细胞上条件性敲除磷酸酶SHP2基因建立的慢性炎症触发增龄型骨衰老模型鼠，观察旋转恒定磁场作用后小鼠运动能力、骨关节组织病理、骨钙含量及骨密度、脊柱关节形态等指标的变化，确定康复疗效；采用血清蛋白质组及代谢组学技术观察有效磁暴露条件下模型鼠血清中蛋白及小分子代谢物的改变；利用高通量基因与蛋白表达芯片技术动态检测磁场对不同年龄阶段模型鼠成骨组织及软骨细胞差异蛋白表达，探索骨衰老发生与磁场康复作用机制。提出具有应用价值的骨衰老的治疗措施与治疗靶点，为临床骨衰老预警与康复提供新策略。

骨衰老是人体衰老早发症状之一，增龄型骨关节疾病与长期慢性炎症刺激相关,本项目组近二十年研究证明磁磁相关物理治疗有效缓解骨质疏松等骨衰老疾病。本项目针对磁增龄型骨关节疾病的康复疗效及作用靶点开展相关研究。建立骨衰老疾病动物模型-T 淋巴细胞上条件性敲除SHP2 小鼠模型骨衰老表型，比较骨衰老小鼠在活动能力、脊柱关节变形、免疫炎症等指标上与骨衰老患者的相似度，观察磁场对骨衰老表征的缓解效应。探讨磁场治疗前后骨衰老小鼠骨衰老进展情况，检测磁场暴露后小鼠发病时间与骨衰老症状与整体表征出现时间差异，评估磁康复效果。采集暴磁前后不同鼠龄阶段野生型鼠和骨衰老小鼠的血清，进行代谢组学分析，筛选并确定差异表达的候选小分子代谢物，并验证关键信号分子调控机制，借助临床骨衰老患者血液与病理样本进一步明确相关信号分子与骨衰老发生发展的相关性。同步拓展骨衰老性疾病骨关节炎及股骨头坏死模型，并完善了旋转恒强磁场在生物物理学上的模拟计算及定量化分析，明确旋转恒强磁场在衰老性骨关节疾病当中减缓血管内皮细胞衰老、软骨细胞凋亡、缓解软骨组织损伤、减轻骨与关节组织炎性作用。结果表明，旋转磁场有助于缓解SHP2-/-小鼠的软骨异常、软骨损伤和骨损伤，并减轻SHP2-/-小鼠骨关节处的炎性损伤；旋转磁场也有利于延缓骨关节炎大鼠关节软骨处的软骨磨损、软骨细胞凋亡和氧化应激损伤；同时，旋转磁场可以减轻实验性脑脊髓膜炎小鼠神经系统的脱髓鞘病变和炎性浸润情况，改善EAE小鼠体内的免疫失衡；旋转磁场还可以减少应激条件下HUVEC的Ca2+超载损伤，并延长HUVEC的寿命和应力条件下秀丽隐杆线虫的寿命，延缓秀丽隐杆线虫的衰老。研究成果为衰老性骨关节疾病如：骨关节炎、股骨头坏死等疾病的治疗提供了新的治疗策略与方法，对于衰老性骨与关节疾病的辅助物理治疗具有重要的学术意义。