摘要： 目的 探讨RANKL/RANK/OPG信号通路对磨损颗粒诱导的小鼠炎性骨溶解的影响。方法 将45只小鼠随机分为对照组、模型组和骨保护素（OPG）组，每组15只，制备小鼠磨损颗粒刺激气囊植骨的骨溶解模型。OPG组小鼠于术后第1天腹腔注射OPG（3 mg/kg），1次/d，对照组和模型组小鼠同期给予等量生理盐水，持续2周。通过HE染色观察气囊植骨壁组织中炎症反应情况；TRAP染色检测气囊植骨壁组织中破骨细胞数目；ELISA检测气囊植骨壁组织中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平；免疫组化检测气囊植骨壁组织中核因子κB受体活化因子配体（RANKL）、核因子κB受体活化因子（RANK）、OPG蛋白阳性表达情况。结果 与对照组比较，模型组气囊植骨组织中多种炎症细胞浸润，存在明显的炎症反应，破骨细胞数、骨溶解面积均增加，IL-6、TNF-α表达水平升高，RANKL、RANK表达增加，而OPG表达减少。与模型组比较，OPG组气囊植骨组织中少量炎症细胞浸润，存在轻度炎症反应，破骨细胞数、骨溶解面积均减少，IL-6、TNF-α表达水平降低，RANKL、RANK表达减少，而OPG表达增加。结论 RANKL/RANK/OPG信号通路可参与调控磨损颗粒诱导的小鼠炎性骨溶解，通过给予外源性OPG能显著抑制磨损颗粒诱导的炎性骨溶解。

RANKL/RANK/OPG信号通路调控磨损颗粒诱导的小鼠炎性骨溶解

张晨¹, 李燕², 郭凤英², 刘子歌¹, 宋国瑞¹, 陈德胜¹

1. 宁夏医科大学总医院脊柱骨科, 银川 750004, 银川 750004;
2. 宁夏医科大学基础医学院生物化学教研室, 银川 750004

收稿日期:2020-05-07出版日期:2021-02-28发布日期:2021-01-21
通讯作者:陈德胜E-mail:charles_cds@163.com
作者简介:张晨(1994-),男,硕士研究生.
基金资助:国家自然科学基金（81760405，81760395，81560364）；宁夏自治区自然科学基金（2018AAC02013）；宁夏医科大学校级课题（XZ2018014）


关键词: RANKL/RANK/OPG信号通路, 白细胞介素-6, 肿瘤坏死因子-α, 磨损颗粒, 骨溶解
Abstract: Objective To explore the effect of RANKL/RANK/OPG signaling pathway on inflammatory osteolysis induced by wear particles in mice. Methods A total of 45 mice were randomly divided into control,model,and osteoprotegerin (OPG) groups (n= 15 each group). The osteolysis model was established by stimulating the bone graft airbags with wear particles. The mice in OPG group were intraperitoneally injected with OPG (3 mg/kg),and those in control and model groups were given the same amount of normal saline for 2 weeks. HE staining was used to observe the inflammation in the bone graft airbag wall. TRAP staining was used to detect the number of osteoclasts. ELISA was used to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels,while immunohistochemistry was used to detect the positive expression of nuclear factor-κB receptor activator ligand (RANKL),nuclear factor-κB receptor activator (RANK),and OPG proteins. Results Compared to the control group,more diverse inflammatory cells were infiltrated in the bone graft tissue and obvious inflammation was found in the model group. Furthermore,osteoclasts and osteolysis area as well as the levels of IL-6,TNF-α,RANKL,and RANK increased,while OPG level decreased. Compared to the model group,mild inflammation reaction and less infiltrated inflammatory cells were observed in OPG group. The osteoclasts and osteolysis area as well as the levels of IL-6,TNF-α,RANKL,and RANK decreased,while OPG level increased. Conclusion The RANKL/RANK/OPG signaling pathway can regulate the inflammatory osteolysis induced by wear particles in mice,which can be significantly inhibited by administering exogenous OPG.
Key words: RANKL/RANK/OPG signaling pathway, interleukin-6, tumor necrosis factor-α, wear particles, osteolysis
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