Joseph W. Galvin, Rachel J. Milam, Brendan M. Patterson, James V. Nepola, Joseph A. Buckwalter, Brian R. Wolf, Felicity M. Say, Katherine E. Free, Elizabeth Yohannes
{"title":"骨膜塑形素是肩关节前方不稳定的生物标志物:滑膜液的蛋白质组分析","authors":"Joseph W. Galvin, Rachel J. Milam, Brendan M. Patterson, James V. Nepola, Joseph A. Buckwalter, Brian R. Wolf, Felicity M. Say, Katherine E. Free, Elizabeth Yohannes","doi":"10.1177/03635465241246258","DOIUrl":null,"url":null,"abstract":"Background:The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury.Hypothesis:Injury-specific factors such as the direction of instability and the severity of glenoid and humeral bone loss are associated with the proteome of synovial fluid in patients with shoulder instability.Study Design:Descriptive laboratory study.Methods:Synovial fluid lavage samples were compared between patients with anterior (n = 12) and posterior (n = 8) instability and those without instability (n = 5). Synovial proteins were identified with liquid chromatography–tandem mass spectrometry. Orthogonal validation of protein targets found to be significant on tandem mass spectrometry was performed in a separate set of prospective patients with Western blotting. Data were processed and analyzed, and P values were adjusted with the Benjamini-Hochberg method for multiple comparisons.Results:A total of 25 patients were included. Tandem mass spectrometry identified 720 protein groups in synovial fluid of patients with shoulder instability. There were 4 synovial proteins that were significantly expressed in patients with anterior instability relative to posterior instability: periostin (POSTN) (adjusted P value = .03; log fold change [logFc] = 4.7), transforming growth factor beta–induced protein ig-h3 (adjusted P value = .05; logFc = 1.7), collagen type VI alpha-3 chain (adjusted P value = .04; logFc = 2.6), and coagulation factor V (adjusted P value = .04; logFc = −3.3). Among these targets, POSTN showed a moderate correlation with the Hill-Sachs lesion size ( r = 0.7). Prospective validation with Western blotting confirmed a significantly higher level of POSTN in synovial fluid of patients with anterior instability ( P = .00025; logFc = 5.1).Conclusion:Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis.Clinical Relevance:Proteomic analysis of synovial fluid in patients with shoulder instability improved our understanding of this abnormality after an injury.","PeriodicalId":517411,"journal":{"name":"The American Journal of Sports Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Periostin Is a Biomarker for Anterior Shoulder Instability: Proteomic Analysis of Synovial Fluid\",\"authors\":\"Joseph W. Galvin, Rachel J. Milam, Brendan M. Patterson, James V. Nepola, Joseph A. Buckwalter, Brian R. Wolf, Felicity M. Say, Katherine E. Free, Elizabeth Yohannes\",\"doi\":\"10.1177/03635465241246258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background:The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury.Hypothesis:Injury-specific factors such as the direction of instability and the severity of glenoid and humeral bone loss are associated with the proteome of synovial fluid in patients with shoulder instability.Study Design:Descriptive laboratory study.Methods:Synovial fluid lavage samples were compared between patients with anterior (n = 12) and posterior (n = 8) instability and those without instability (n = 5). Synovial proteins were identified with liquid chromatography–tandem mass spectrometry. Orthogonal validation of protein targets found to be significant on tandem mass spectrometry was performed in a separate set of prospective patients with Western blotting. Data were processed and analyzed, and P values were adjusted with the Benjamini-Hochberg method for multiple comparisons.Results:A total of 25 patients were included. Tandem mass spectrometry identified 720 protein groups in synovial fluid of patients with shoulder instability. There were 4 synovial proteins that were significantly expressed in patients with anterior instability relative to posterior instability: periostin (POSTN) (adjusted P value = .03; log fold change [logFc] = 4.7), transforming growth factor beta–induced protein ig-h3 (adjusted P value = .05; logFc = 1.7), collagen type VI alpha-3 chain (adjusted P value = .04; logFc = 2.6), and coagulation factor V (adjusted P value = .04; logFc = −3.3). Among these targets, POSTN showed a moderate correlation with the Hill-Sachs lesion size ( r = 0.7). Prospective validation with Western blotting confirmed a significantly higher level of POSTN in synovial fluid of patients with anterior instability ( P = .00025; logFc = 5.1).Conclusion:Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis.Clinical Relevance:Proteomic analysis of synovial fluid in patients with shoulder instability improved our understanding of this abnormality after an injury.\",\"PeriodicalId\":517411,\"journal\":{\"name\":\"The American Journal of Sports Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-05-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The American Journal of Sports Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/03635465241246258\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American Journal of Sports Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/03635465241246258","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景:人们对急性和慢性肩关节不稳定时肩关节滑膜微环境中可能导致关节退行性变的渐进生物变化知之甚少。假设:损伤的特异性因素(如不稳定性的方向、盂骨和肱骨损失的严重程度)与肩关节不稳定患者滑液的蛋白质组有关。研究设计:描述性实验室研究。方法:比较前方(12人)和后方(8人)不稳定患者与无不稳定患者(5人)的滑膜液灌洗样本。采用液相色谱-串联质谱法鉴定滑膜蛋白质。对串联质谱法发现的重要蛋白质靶点,在另一组前瞻性患者中用 Western 印迹法进行了正交验证。对数据进行了处理和分析,并用本杰明-霍奇伯格法(Benjamini-Hochberg method)调整了多重比较的P值。串联质谱法在肩关节不稳定患者的滑液中发现了720种蛋白质。与后侧不稳患者相比,前侧不稳患者有4种滑膜蛋白表达量明显增加:骨膜增生蛋白(POSTN)(调整后P值=0.03;对数折叠变化[logFc] = 4.7)、转化生长因子 beta 诱导蛋白 ig-h3(调整后 P 值 = .05;logFc = 1.7)、VI 型胶原蛋白 alpha-3 链(调整后 P 值 = .04;logFc = 2.6)和凝血因子 V(调整后 P 值 = .04;logFc = -3.3)。在这些靶点中,POSTN 与 Hill-Sachs 病变大小呈中度相关(r = 0.7)。结论:蛋白质组分析丰富了我们对分泌到肩关节不稳定患者肩关节滑液中的蛋白质的了解。POSTN是一种与组织重塑和修复有关的促炎性分解代谢蛋白,它是肩关节前侧不稳定的一个重要靶点,这一发现很新颖。临床意义:对肩关节不稳定患者滑液的蛋白质组分析提高了我们对损伤后滑液异常的认识。
Periostin Is a Biomarker for Anterior Shoulder Instability: Proteomic Analysis of Synovial Fluid
Background:The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury.Hypothesis:Injury-specific factors such as the direction of instability and the severity of glenoid and humeral bone loss are associated with the proteome of synovial fluid in patients with shoulder instability.Study Design:Descriptive laboratory study.Methods:Synovial fluid lavage samples were compared between patients with anterior (n = 12) and posterior (n = 8) instability and those without instability (n = 5). Synovial proteins were identified with liquid chromatography–tandem mass spectrometry. Orthogonal validation of protein targets found to be significant on tandem mass spectrometry was performed in a separate set of prospective patients with Western blotting. Data were processed and analyzed, and P values were adjusted with the Benjamini-Hochberg method for multiple comparisons.Results:A total of 25 patients were included. Tandem mass spectrometry identified 720 protein groups in synovial fluid of patients with shoulder instability. There were 4 synovial proteins that were significantly expressed in patients with anterior instability relative to posterior instability: periostin (POSTN) (adjusted P value = .03; log fold change [logFc] = 4.7), transforming growth factor beta–induced protein ig-h3 (adjusted P value = .05; logFc = 1.7), collagen type VI alpha-3 chain (adjusted P value = .04; logFc = 2.6), and coagulation factor V (adjusted P value = .04; logFc = −3.3). Among these targets, POSTN showed a moderate correlation with the Hill-Sachs lesion size ( r = 0.7). Prospective validation with Western blotting confirmed a significantly higher level of POSTN in synovial fluid of patients with anterior instability ( P = .00025; logFc = 5.1).Conclusion:Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis.Clinical Relevance:Proteomic analysis of synovial fluid in patients with shoulder instability improved our understanding of this abnormality after an injury.