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.

中文翻译：

---

骨膜素是肩前部不稳定的生物标志物：滑液的蛋白质组学分析

背景：在急性和慢性不稳定性中，肩部滑膜微环境的增量生物学变化可能导致关节退化，但人们对此知之甚少。对肩关节不稳患者的滑液进行蛋白质组学分析可能会提高我们对受伤后流入肩关节滑液中的蛋白质的理解。假设：损伤特异性因素（例如不稳定的方向以及关节盂和肱骨骨质流失的严重程度）相关研究设计：描述性实验室研究。方法：比较肩关节前部不稳定 (n = 12) 和后部不稳定 (n = 8) 患者与无不稳定患者 (n = 8) 的滑液灌洗样本= 5）。通过液相色谱-串联质谱法鉴定滑膜蛋白。在一组单独的前瞻性患者中使用蛋白质印迹法对串联质谱法中发现显着的蛋白质靶点进行了正交验证。对数据进行处理和分析，并采用Benjamini-Hochberg法调整P值进行多重比较。结果：共纳入25例患者。串联质谱法鉴定了肩关节不稳患者滑液中的 720 个蛋白质组。相对于后部不稳定性，有 4 种滑膜蛋白在前部不稳定性患者中显着表达：骨膜蛋白 (POSTN)（调整后的 P 值 = .03；对数倍数变化 [logFc] = 4.7）、转化生长因子 β 诱导的蛋白 ig- h3（调整后的 P 值 = .05；logFc = 1.7）、VI 型胶原蛋白 alpha-3 链（调整后的 P 值 = .04；logFc = 2.6）和凝血因子 V（调整后的 P 值 = .04；logFc = -3.3 ）。在这些目标中，POSTN 显示与 Hill-Sachs 病变大小具有中等相关性 (r = 0.7)。蛋白质印迹的前瞻性验证证实，前不稳定患者滑液中的 POSTN 水平显着较高（P = .00025；logFc = 5.1）。结论：蛋白质组分析丰富了我们对前不稳定患者肩关节滑液中分泌的蛋白质的理解。肩部不稳定。 POSTN（一种参与组织重塑和修复的促炎分解代谢蛋白）被鉴定为肩部前不稳定的重要靶点是一项新发现。因此，有必要进一步研究以确定 POSTN 在骨质流失和创伤后骨关节炎进展中可能发挥的作用。临床相关性：对肩关节不稳患者滑液的蛋白质组学分析提高了我们对受伤后这种异常的理解。