VETERM, Equine Surgery Unit, Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.
Int J Mol Sci. 2021 May 25;22(11):5619. doi: 10.3390/ijms22115619.
Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.
腱病是一种痛苦且使人丧失能力的病症，影响着 25%的成年人口。为了满足对现实大型动物模型的需求，我们在此提出了一种羊的肌腱损伤模型，用于比较研究成年瘢痕修复和胎儿再生。研究表明，胎儿肌腱在 28 天内即可完全再生，而成年肌腱缺陷在损伤后五个月仍在宏观和组织学上明显存在。除了进行全面的组织学评估外，还对分泌组的蛋白质组进行了分析。与组织学数据一致，在成年肌腱缺陷中观察到特定且明显的炎症，伴随着中性粒细胞的激活，这得到了促炎因子、中性粒细胞趋化因子的显著上调、潜在组织损伤的抗菌和细胞外基质降解酶的释放以及对氧化应激的反应的证实。相比之下，受伤胎儿肌腱的分泌蛋白包括启动炎症消退或促进功能性细胞外基质产生的蛋白。这些结果证明了我们新型羊胎儿肌腱再生模型的强大功能和相关性，这有望加速该领域的研究。该模型的初步研究结果支持了我们对成功的胎儿肌腱愈合过程的分子理解，并可能为改进的治疗策略提供指导。
