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去泛素化酶圆柱瘤蛋白在关节软骨和软骨下骨中的表达与膝关节骨关节炎的严重程度相关。

Expression of the deubiquitinase cylindromatosis in articular cartilage and subchondral bone is associated with the severity of knee osteoarthritis.

作者信息

Hong Liu, Shanjiang Yu, Qian Wang, Chunguo Li, Fei Zhou, Jinming Yu, Jiyou Gao, Na Li, Yang Li, Feng Du

机构信息

Department of Orthopedics, People's Hospital of Linzi, Zibo, Shandong 255400, P.R. China.

Department of Orthopedics, Shandong Provincial Hospital, Jinan, Shandong 250021, P.R. China.

出版信息

Exp Ther Med. 2017 Dec;14(6):5990-5996. doi: 10.3892/etm.2017.5326. Epub 2017 Oct 18.

Abstract

Cylindromatosis (CYLD) is a deubiquitinating enzyme that regulates multiple key signaling pathways involved in the pathophysiology of knee osteoarthritis (KOA). Previous studies have indicated that the expression of CYLD in the articular cartilage of patients with KOA is significantly higher than in healthy controls. However, limited data are available regarding the association between CYLD expression and the severity of KOA. The aim of the present study was to investigate the association between CYLD expression in joint tissues and the severity of KOA. A total of 156 individual tibial plateau samples were obtained between January 2011 and January 2016 from patients that had undergone total knee arthroplasty due to KOA or from healthy controls. The severity of KOA was evaluated using the Kellgren Lawrence (KL) and Mankin scoring systems. Additionally, CYLD expression in the articular cartilage and subchondral bone was analyzed using immunohistochemistry. Compared with the healthy controls, patients with KOA exhibited significantly increased CYLD levels in the articular cartilage (6.53±2.01 vs. 28.69±13.23, P<0.001) and significantly decreased CYLD levels in the subchondral bone (11.46±2.34 vs. 3.50±2.54, P<0.001). Correlation analysis indicated that CYLD expression in the articular cartilage was positively correlated with the KL (=0.837, P<0.001) and Mankin scores (=0.925, P<0.001), while its expression in the subchondral bone was negatively correlated with the KL (=-0.802, P<0.001) and Mankin scores (=-0.844, P<0.001). The results of the present study demonstrate that CYLD levels in the articular cartilage and subchondral bone are associated with the severity of KOA. Thus, CYLD may be a potential diagnostic and predictive biomarker for KOA and a novel target in its treatment.

摘要

圆柱瘤病(CYLD)是一种去泛素化酶,可调节参与膝关节骨关节炎(KOA)病理生理学的多个关键信号通路。先前的研究表明,KOA患者关节软骨中CYLD的表达明显高于健康对照组。然而,关于CYLD表达与KOA严重程度之间的关联,现有数据有限。本研究的目的是探讨关节组织中CYLD表达与KOA严重程度之间的关联。2011年1月至2016年1月期间,共采集了156份个体胫骨平台样本,这些样本来自因KOA接受全膝关节置换术的患者或健康对照组。使用Kellgren Lawrence(KL)和Mankin评分系统评估KOA的严重程度。此外,采用免疫组织化学方法分析关节软骨和软骨下骨中CYLD的表达。与健康对照组相比,KOA患者关节软骨中CYLD水平显著升高(6.53±2.01对28.69±13.23,P<0.001),而软骨下骨中CYLD水平显著降低(11.46±2.34对3.50±2.54,P<0.001)。相关性分析表明,关节软骨中CYLD表达与KL评分(=0.837,P<0.001)和Mankin评分(=0.925,P<0.001)呈正相关,而其在软骨下骨中的表达与KL评分(=-0.802,P<0.001)和Mankin评分(=-0.844,P<0.001)呈负相关。本研究结果表明,关节软骨和软骨下骨中的CYLD水平与KOA的严重程度相关。因此,CYLD可能是KOA的潜在诊断和预测生物标志物,也是其治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d40/5740750/3c8d2d36d48d/etm-14-06-5990-g00.jpg

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