Regenerative functions of exosomes rely on their contents which are influenced by pathological stimuli, including hypoxia, in rotator cuff tendon injuries (RCTI). The hypoxic environment triggers tenocytes and adjacent adipose-derived mesenchymal stem cells (ADMSCs) to release regenerative mediators to the ECM via the exosomes which elicit autocrine/paracrine responses to protect the tendon matrix from injury. We investigated the exosomal protein contents from tenocytes and subcutaneous ADMSCs from the shoulder of Yucatan microswine cultured under hypoxic conditions (2% O2). The exosomal proteins were detected using high-resolution mass spectrometry nano-LC-MS/MS Tribrid system and were compiled using 'Scaffold' software. Hypoxic exosomes from tenocytes and ADMSCs carried 199 and 65 proteins, respectively. The key proteins identified by mass spectrometry and associated with ECM homeostasis from hypoxic ADMSCs included MMP2, COL6A, CTSD and TN-C and those from hypoxic tenocytes were THSB1, NSEP1, ITIH4 and TN-C. These findings were confirmed at the mRNA and protein level in the hypoxic ADMSCs and tenocytes. These proteins are involved in multiple signaling pathways of ECM repair/regeneration. This warrants further investigations for their translational significance in the management of RCTI.

中文翻译：

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缺氧触发的肩膀肌腱细胞和脂肪来源的间充质干细胞的外泌体中的基质再生蛋白。

肩袖腱损伤（RCTI）中，外泌体的再生功能取决于其内容物的含量，这些内容物受包括缺氧在内的病理刺激的影响。低氧环境触发肌腱细胞和相邻的脂肪间充质干细胞（ADMSC）通过外泌体释放再生介体至ECM，外泌体引起自分泌/旁分泌反应以保护肌腱基质免受损伤。我们调查了在缺氧条件下（2％O2）培养的尤卡坦微猪肩部肌腱细胞和皮下ADMSCs的外泌体蛋白含量。使用高分辨率质谱法纳米LC-MS / MS Tribrid系统检测外泌体蛋白，并使用“ Scaffold”软件对其进行编译。来自肌腱细胞和ADMSC的低氧外泌体分别携带199和65种蛋白质。质谱鉴定的与低氧ADMSCs的ECM稳态相关的关键蛋白包括MMP2，COL6A，CTSD和TN-C，而来自低氧肌腱细胞的蛋白为THSB1，NSEP1，ITIH4和TN-C。这些发现在低氧ADMSC和肌腱细胞的mRNA和蛋白水平得到了证实。这些蛋白质参与ECM修复/再生的多种信号通路。这值得进一步研究其在RCTI管理中的翻译意义。