{"title":"Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis.","authors":"Wanvisa Udomsinprasert, Natcha Mookkhan, Thanyalak Tabtimnark, Teerapong Aramruang, Tachatra Ungsudechachai, Wacharapol Saengsiwaritt, Jiraphun Jittikoon, Usa Chaikledkaew, Sittisak Honsawek","doi":"10.1302/2046-3758.136.BJR-2023-0180.R1","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.</p><p><strong>Methods: </strong>A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.</p><p><strong>Results: </strong>COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that <i>COMP</i> mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative <i>COMP</i> mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, <i>COMP</i> mRNA expression was considerably up-regulated in a time-dependent manner.</p><p><strong>Conclusion: </strong>All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"261-271"},"PeriodicalIF":4.7000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142849/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone & Joint Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1302/2046-3758.136.BJR-2023-0180.R1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.
Methods: A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.
Results: COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner.
Conclusion: All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.
目的:本研究旨在确定一种软骨蛋白--软骨低聚基质蛋白(COMP)在膝关节骨性关节炎(OA)患者中的表达及临床意义:方法:共招募了 270 名膝关节 OA 患者和 93 名健康对照者。采用酶联免疫吸附测定法、实时聚合酶链反应和免疫组化法测定膝关节OA患者血清、滑膜液、滑膜组织和成纤维细胞样滑膜细胞(FLSs)中COMP信使RNA(mRNA)和蛋白质水平:结果:膝关节 OA 患者血清和滑液中的 COMP 蛋白水平明显升高,尤其是晚期患者。血清中的COMP与放射学严重程度以及身体成分、体能、膝关节疼痛和残疾程度都有明显的相关性。接收者操作特征曲线分析显示,血清COMP作为膝关节OA的生物标记物具有诊断价值(41.64纳克/毫升,曲线下面积(AUC)= 1.00),灵敏度为99.6%,特异性为100.0%。进一步分析发现,COMP mRNA在膝关节OA炎症滑膜中的表达明显上调,这与免疫组化染色显示的COMP蛋白在膝关节OA炎症滑膜的衬里层和衬里下层的定位一致。最值得注意的是,膝关节 OA 滑膜中 COMP mRNA 的相对表达与膝关节 OA 患者血清和滑液中的蛋白水平呈正相关。在被肿瘤坏死因子-α激活的人类膝关节OA FLS中,COMP mRNA的表达以时间依赖的方式显著上调:所有结果表明,COMP 可作为膝关节 OA 的辅助诊断标志物,与标准诊断方法结合使用。