RANKL在颞下颌关节软骨退变中的作用

doi:10.19438/j.cjoms.2017.02.001

中国口腔颌面外科杂志 ›› 2017, Vol. 15 ›› Issue (2): 97-102.doi: 10.19438/j.cjoms.2017.02.001

• 论著 • 下一篇

RANKL在颞下颌关节软骨退变中的作用

范宝婷^{1, 2*, *}, 徐伟峰^{1*, *}, 沈佩¹, 李慧萍¹, 赵华强, 张善勇

1.上海交通大学医学院附属第九人民医院·口腔医学院口腔外科, 上海市口腔医学重点实验室,上海 200011;
2.山东大学口腔医学院口腔颌面外科,山东济南 250012

收稿日期:2016-09-20 出版日期:2017-03-20 发布日期:2017-04-13
通讯作者: 张善勇,E-mail: zhangshanyong@126.com;赵华强，E-mail:zhaoha@sdu.edu.cn
作者简介:范宝婷（1991-）,女,硕士,E-mail: 18769782652@163.com;徐伟峰（1989-）,男,硕士,E-mail:xwf19891215@163.com。*并列第一作者

Effect of RANKL on chondrocyte differentiation of temporomandibular joint

FAN Bao-ting^{1, 2}, XU Wei-feng¹, SHEN Pei¹, LI Hui-ping¹, ZHAO Hua-qiang², ZHANG Shan-yong¹

1.Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Stomatology. Shanghai 200011;
2.Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University. Jinan 250012, Shandong Province, China

Received:2016-09-20 Online:2017-03-20 Published:2017-04-13
Contact: 国家自然科学基金（81371168,81671010）; 上海交通大学医工交叉项目（YG2013MS63）; 上海市教育委员会高峰-高原学科-上海交通大学医学院“研究型医师”项目（20152226）; 上海交通大学医学院转化医学创新基金（15ZH2007）; 上海市科学技术委员会生物医药支撑项目（16441908800）; 上海市卫生和计划生育委员会重点项目（201640001）; 科技部国家重点研发计划项目（2016YFC1100600）

摘要/Abstract

摘要： 目的明确RANKL对软骨的直接作用,为颞下颌关节软骨退变的治疗提供新思路。方法体外ATDC5细胞实验,明确RANKL对软骨细胞的作用。体外培养牛软骨片,明确RANKL对软骨组织的作用。Western 蛋白印迹检测细胞中ADAMTS5、MMP13、RANK的表达,RT-qPCR检测细胞中Col2a1、Col10a、RANK、RANKL、MMP13、ADAMTS5的表达,Alcian蓝和Safranin O染色及Mankin评分分析软骨组织的破坏程度。采用SPSS17.0软件包对数据进行统计学分析。结果在软骨分化过程中,RANKL和RANK的表达随时间增多（P<0.05）。外源性RANKL刺激可使软骨细胞的RANK上调。相对于对照组,RANKL刺激后的ATDC5细胞中与软骨退变相关的蛋白MMP13和ADAMTS5的表达显著升高,且呈浓度依赖性（P<0.05）。而软骨标志因子II型胶原和X型胶原的mRNA水平显著下降（P<0.05）。体外培养牛软骨片发现,外源性RANKL刺激可导致软骨基质降解,结构紊乱,蛋白多糖丢失（P<0.05）。结论软骨细胞可分泌RANKL和RANK。RANKL可诱导ADAMTS5表达增高,直接诱导软骨细胞退变。因此,可以RANKL为干预靶点,作为预防和治疗颞下颌关节软骨退变的新途径。

关键词: 颞下颌关节, 髁突吸收, 软骨退变, RANKL

Abstract: PURPOSE : This study was aimed to identify a novel therapeutic way for joint cartilage degeneration. METHODS : By using ATDC5 chondrogenic cells and bovine cartilages, we studied the role of RANKL in cartilage degeneration in vitro. The protein expression of MMP13, RANK, RANKL and ADAMTS5 was detected using Western blot. The mRNA expression of Col2a1, Col10a, MMP13, RANK and ADAMTS5 was detected using RT-qPCR. Degeneration of cartilage was analyzed by safranin O and alician blue staining and Mankin score. The data were analyzed by paired t test using SPSS17.0 software package. RESULTS : The results of real time PCR confirmed that both RANK and RANKL were dynamically expressed in ATDC5 cells during all differentiation phases (P<0.05). RANK protein expression was significantly enhanced by RANKL treatment for 48 h in comparison to that for 0h. The mRNA and protein level of ADAMTS5 was significantly increased as stimulated by RANKL compared with the control over time (P<0.05). In addition, vacuolation and degeneration were observed in bovine cartilages with RANKL stimulation (P<0.05). CONCLUSION S: RANKL contributes to cartilage degeneration in condylar resorption and inhibition of this pathway may be a useful strategy for condylar resorption treatment.

中图分类号:

R786.2

范宝婷, 徐伟峰, 沈佩, 李慧萍, 赵华强, 张善勇. RANKL在颞下颌关节软骨退变中的作用[J]. 中国口腔颌面外科杂志, 2017, 15(2): 97-102.

FAN Bao-ting, XU Wei-feng, SHEN Pei, LI Hui-ping, ZHAO Hua-qiang, ZHANG Shan-yong. Effect of RANKL on chondrocyte differentiation of temporomandibular joint[J]. China J Oral Maxillofac Surg, 2017, 15(2): 97-102.

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RANKL在颞下颌关节软骨退变中的作用

Effect of RANKL on chondrocyte differentiation of temporomandibular joint

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