钛金属离子介导骨溶解机制中的炎症反应-STAT信号通路  

Inflammatory reactions-STAT signaling pathway in the mechanism underlying titanium metal ion-mediated osteolysis

作　　者：赵文杰[1] 戴闽[1] 张斌 万细珍[1] 范红先[1] 

机构地区：[1]南昌大学第一附属医院骨科,江西省南昌市330006 [2]江西省人工关节工程技术研究中心,江西省南昌市330006

出　　处：《中国组织工程研究》2016年第4期492-496,共5页Chinese Journal of Tissue Engineering Research

基　　金：江西省教育厅科学技术研究项目(GJJ12067);江西省科技厅指导性计划(2010ZDS00700)~~

摘　　要：背景:抑制骨溶解是减少人工置换假体松动的重要手段,但目前对骨溶解的发生机制尚不明确。目的:分析炎症反应-JAK/STAT信号转导通路与钛金属离子介导骨溶解的相关性。方法:将50只昆明小鼠随机分为5组,假手术组向暴露的颅盖骨中注射生理盐水;其余4组向暴露的颅盖骨中注射钛金属磨损微粒混悬液,制备颅盖骨溶解模型,造模第2天选择其中3组分别腹腔注射低、中、高剂量的(1,10,100μmol/L)JAK抑制剂AG490 10 mL/kg,1次/d。28 d后,检测各组颅盖骨组织骨溶解面积及破骨细胞数,炎症因子肿瘤坏死因子α、血管内皮生长因子及白细胞介素10水平,JAK1/2/3与STAT1/3蛋白的表达,细胞凋亡蛋白Caspase3/9蛋白的表达。结果与结论:(1)与假手术组相比,模型组小鼠骨溶解面积明显增大(P<0.01),破骨细胞数明显增多,各炎症因子水平明显升高(P<0.01),JAK/STAT信号通路蛋白及细胞凋亡蛋白表达明显升高(P均<0.01)。(2)与模型组相比,中、高剂量AG490组骨溶解面积降低,破骨细胞数量减少,各炎症因子水平明显减少,JAK/STAT信号通路蛋白及细胞凋亡蛋白表达明显减少(P均<0.01)。(3)表明JAK抑制剂AG490可通过抑制炎症反应-JAK/STAT信号通路,改善钛金属离子介导的骨溶解病理过程。BACKGROUND： Inhibition of osteolysis is an important manner to reduce prosthesis loosening, but the mechanism of osteolysis is still unclear. OBJECTIVE： To analyze the correlation of inflammatory reaction-JAK/STAT signal transduction pathway and titanium metal ion-mediated osteolysis. METHODS： A total of 50 Kunming mice were divided into five groups. In the sham group, the cranium was injected with physiological saline. In other four groups, the cranium was injected with titanium metal wear particle suspension to establish models of calvarial osteolysis. On day 2 after model establishment, mice in three groups were separately intraperitoneally injected with low-, moderate- and high-dose（1, 10, 100 μmol/L） JAK inhibitor AG490 10 m L/kg, once a day. 28 days later, osteolysis area, number of osteoclasts, tumor necrosis factor α, vascular endothelial growth factor and interleukin-10 levels, JAK1/2/3 and STAT1/3 protein expression, andCaspase3/9 protein expression were detected in each group. RESULTS AND CONCLUSION：（1） Compared with the sham surgery group, osteolysis area of mice was significantly larger in the model group（P〈0.01）, and the number of osteoclast was significantly more, and inflammatory factor levels were significantly higher（P〈0.01）. JAK/STAT signaling pathway protein and apoptotic protein expressions were significantly higher（all P〈0.01）.（2） Compared with the model group, osteolysis area was smaller, the number of osteoclasts was less, inflammatory factor levels were significantly less, JAK/STAT signaling pathway protein and apoptotic protein expression was significantly less in the moderate- and high-dose AG490 groups（all P〈0.01）.（3） These findings suggested that JAK inhibitor AG490 alleviates titanium metal ion-mediated osteolysis by inhibiting inflammatory reactions and JAK/STAT signaling transduction pathway.

关 键 词：骨质溶解 炎症 破骨细胞 组织工程 骨科植入物 人工假体 磨损微粒 炎症反应 JAK/STAT信号通路 骨溶解 细胞凋亡 病理过程 

分 类 号：R318[医药卫生—生物医学工程]