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Osteopontin Level in Synovial Fluid is Associated with the Severity of Joint Pain and Cartilage Degeneration After Anterior Cruciate Ligament Rupture

滑液中的骨桥蛋白水平与前十字韧带断裂后关节疼痛和软骨退化的严重程度相关

基本信息

批准号：
22600002
负责人：
JYU Neishin
金额：
$ 2.83万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Osteopontin (OPN) is an O-glycosylated phosphoprotein which is synthesized in a variety of tissues and cells including chondrocytes and synoviocytes. Accumulating data indicated that OPN is involved in the process of inflammation, immunity, and bone metabolism. OPN knockout mice have already been created and shown that cartilage degradation is accelerated in the absence of OPN. Human studies revealed that OPN protein level increased in the synovial fluid from the patients suffering from OA and RA. These data strongly suggest that OPN is involved in joint homeostasis and in the pathogenesis of arthritis. However, the molecular functions of OPN in these processes are not yet extensively studied. Here we report that synovial fluid OPN level is associated with the severity of joint pain.This study was approved by the Ethics Committee of this institute. All patients included in this study gave their full, written, informed consent for participation prior to the operative procedure. Tissue s … More amples (synovial fluid and synovial membrane) were obtained from the patients who underwent anterior cruciate ligament reconstruction (ACL-R) from January 2009 till October 2011 in our hospital. OPN mRNA expressed in synovial membrane was quantified by RT-QPCR (Roche, Light Cycler 480, Germany). Total OPN protein levels in synovial fluid were quantified using OPN/OPN N-half ELISA kit (IBL, Japan) and compared them with clinical parameters such as Lysholm score, visual analogue scale (VAS), serum C-reactive protein (CRP) level, and macroscopic observation of cartilage degradation.As previously reported, OPN mRNA expression level in synovial membrane and OPNprotein level in synovial fluid were significantly increased in OA if compared with those of ACL-R.In the ACL-R group, OPN protein level in synovial fluid was gradually decreased after the injury. We found that OPN protein level in synovial fluid was POSITIVELY associated with the severity of joint pain (VAS). Since OPN acts as a pro-inflammatory cytokines by enhancing migration, survival, phagocytosis, and pro-inflammatory cytokine production of macrophages, we hypothesized that OPN induces joint pain by promoting inflammation in the joint. To test this hypothesis, we investigated the correlation of OPN protein level in synovial fluid with serum CRP level. However, we did not observe any correlation between these two. However, OPN level was positively correlated with the volume of synovial fluid, a marker for joint inflammation. Less

骨桥蛋白（OPN）是一种O-糖基化的磷蛋白，在软骨细胞和滑膜细胞等多种组织和细胞中合成。越来越多的研究表明骨桥蛋白参与炎症、免疫和骨代谢过程。已经建立了OPN敲除小鼠，并显示在没有OPN的情况下软骨降解加速。人体研究表明，骨桥蛋白水平增加，在滑液从患有OA和RA。这些数据有力地表明，骨桥蛋白参与关节稳态和关节炎的发病机制。然而，OPN在这些过程中的分子功能尚未得到广泛研究。我们在此报告滑液OPN水平与关节疼痛的严重程度相关。本研究中纳入的所有患者在手术前均提供了完整的书面知情同意书。组织s ...更多信息方法收集2009年1月至2011年10月在我院行前交叉韧带重建术（ACL-R）的患者的关节液和滑膜标本。通过RT-QPCR（Roche，Light Cycler 480，德国）定量滑膜中表达的OPN mRNA。使用OPN/OPN N-half ELISA试剂盒定量滑液中的总OPN蛋白水平（IBL，日本），并将其与临床参数如Lysholm评分、视觉模拟评分（VAS）、血清C-反应蛋白（CRP）水平和软骨降解的宏观观察进行比较。与ACL-R组相比，OA组滑膜中OPN mRNA表达水平和滑液中OPN蛋白水平均显著升高。伤后关节液中OPN蛋白水平逐渐下降。我们发现关节液中OPN蛋白水平与关节疼痛的严重程度（VAS）呈正相关。由于OPN通过增强巨噬细胞的迁移、存活、吞噬作用和促炎细胞因子产生而充当促炎细胞因子，因此我们假设OPN通过促进关节中的炎症而诱导关节疼痛。为了验证这一假设，我们研究了关节液中OPN蛋白水平与血清CRP水平的相关性。然而，我们没有观察到这两者之间的任何相关性。然而，骨桥蛋白水平与关节液量（关节炎症的标志物）呈正相关。少