CCL22 是软骨损伤的生物标志物，在软骨细胞凋亡中发挥功能作用。

CCL22 is a biomarker of cartilage injury and plays a functional role in chondrocyte apoptosis.

机构信息

McCaig Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta, Canada.

Department of Physical Therapy, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada; Glen Sather Sports Medicine Clinic, University of Alberta, Edmonton, Alberta, Canada; Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.

出版信息

Cytokine. 2019 Mar;115:32-44. doi: 10.1016/j.cyto.2018.11.030. Epub 2019 Jan 7.

DOI:10.1016/j.cyto.2018.11.030

PMID:30623804

Abstract

BACKGROUND

Osteoarthritis (OA) is one of the leading causes of disability worldwide. Previous history of knee injury is a significant risk factor for OA. It has been established that low-level chronic inflammation plays a pivotal role in the onset and pathogenesis of OA. The primary aim of this research was to determine if a history of knee joint injury is associated with systemic inflammation. A secondary aim was to determine if systemic inflammation is related to knee pain and joint structure.

METHODS

Differences in serum cytokine association networks, knee joint structural changes (MRI), and self-reported pain (i.e., Knee Injury and Osteoarthritis Outcome Score Pain subscale, KOOS and Intermittent and Constant Osteoarthritis Pain score, ICOAP) between individuals who had sustained a youth (aged 15-26 years) sport-related knee injury 3-10 years previously and age- and sex-matched controls were examined. Proteins of interest were also examined in an OA rat model.

RESULTS

Cytokine association networks were found to differ significantly between study groups, yet no significant associations were found between networks and KOOS or MRI-defined OA. A group of cytokines (MCP1/CCL2, CCL22 and TNFα) were differentially associated with other cytokines between study groups. In a pre-clinical rat OA model, serum CCL22 levels were associated with pain (r = 0.255, p = 0.045) and structural changes to the cartilage. CCL22 expression was also observed in human OA cartilage and furthermore, CCL22 induced apoptosis of isolated human chondrocytes.

DISCUSSION

These results suggest that CCL22 may be an early factor in the onset/pathogenic process of cartilage degeneration and/or related to pain OA.

摘要

背景

骨关节炎（OA）是全球导致残疾的主要原因之一。膝关节既往损伤史是 OA 的一个重要危险因素。已经证实，低水平的慢性炎症在 OA 的发病和发病机制中起关键作用。本研究的主要目的是确定膝关节损伤史是否与全身炎症有关。次要目的是确定全身炎症是否与膝关节疼痛和关节结构有关。

方法

比较既往（3-10 年前）有青年（15-26 岁）运动相关膝关节损伤史且年龄和性别匹配的个体与对照组之间的血清细胞因子关联网络、膝关节结构变化（MRI）和自我报告的疼痛（即膝关节损伤和骨关节炎结局评分疼痛子量表、KOOS 和间歇性和持续性骨关节炎疼痛评分、ICOAP）差异。还在 OA 大鼠模型中检查了感兴趣的蛋白质。

结果

研究组之间的细胞因子关联网络存在显著差异，但网络与 KOOS 或 MRI 定义的 OA 之间没有显著关联。一组细胞因子（MCP1/CCL2、CCL22 和 TNFα）在研究组之间与其他细胞因子存在差异关联。在临床前大鼠 OA 模型中，血清 CCL22 水平与疼痛（r=0.255，p=0.045）和软骨结构变化相关。在人 OA 软骨中也观察到 CCL22 的表达，并且 CCL22 诱导分离的人软骨细胞凋亡。