中国组织工程研究

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (4): 492-496.doi: 10.3969/j.issn.2095-4344.2016.04.007

• 人工假体 artificial prosthesis • 上一篇    下一篇

钛金属离子介导骨溶解机制中的炎症反应-STAT信号通路

赵文杰1，戴 闽1，张 斌2，万细珍1，范红先1   

  1. 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
  • 收稿日期:2015-11-19 出版日期:2016-01-22 发布日期:2016-01-22
  • 通讯作者: 范红先，南昌大学第一附属医院骨科，江西省南昌市 330006
  • 作者简介:赵文杰，男，1988年生，江西省南昌市人，2015年南昌大学毕业，硕士，主要从事骨科、人工关节置换与生物力学研究。
  • 基金资助:
    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)

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

Zhao Wen-jie1, Dai Min1, Zhang Bin2, Wan Xi-zhen1, Fan Hong-xian1   

  1. 1Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China; 2Jiangxi Province Artificial Joint Engineering Technology Research Center, Nanchang 330006, Jiangxi Province, China
  • Received:2015-11-19 Online:2016-01-22 Published:2016-01-22
  • Contact: Fan Hong-xian, Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • About author:Zhao Wen-jie, Master, Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • Supported by:

    the Science and Technology Research Project of Jiangxi Provincial Department of Education, No. GJJ12067; the Jiangxi Provincial Science and Technology Department Guidance Plan, No. 2010ZDS00700

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摘要：

文章快速阅读：

文题释义：

炎症反应：是机体内最常见的病理过程，也是多种骨组织病理过程的共同信号通路，如成骨细胞的增殖、迁移和分化及骨密度的变化。

STAT信号转导通路：是细胞内最常见的信号转导通路之一，且已有研究表明该信号通路与骨组织的多种病理学过程相关，可作为干预骨溶解过程的重要靶点。

 

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(1，10，100 μmol/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。 

关键词: 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, 破骨细胞, 细胞凋亡, 病理过程

Abstract:

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 mL/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, and Caspase3/9 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.