Department of Biomedical Engineering, University of Rochester, Rochester, New York.
Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York.
Ann N Y Acad Sci. 2019 Apr;1442(1):118-127. doi: 10.1111/nyas.14013. Epub 2019 Feb 27.
Adult tendons heal as scar tissue, whereas embryonic tendons heal scarlessly via unknown mechanisms. Scarred tendon healing results from inflammation-driven imbalances in anabolic and catabolic functions. To test scarless versus scarring age tendon cell responses to inflammatory conditions, we treated embryonic and postnatal tendon cells with interleukin (IL)-1β and characterized expression of collagens, matrix metalloproteinases (MMPs), inflammatory mediators, and phosphorylation of signaling molecules. At baseline, postnatal cells expressed significantly higher levels of inflammatory mediators. When treated with IL-1β, both postnatal and embryonic cells upregulated inflammatory mediators and MMPs. Notably, postnatal cells secreted inflammatory factors up to 12.5 times the concentration in embryonic cultures. IL-1β activated NF-κB p65 and p38 mitogen-activated protein kinase (MAPK) pathways in both cell types, but phosphorylated p38 MAPK levels were two times higher in postnatal than embryonic cells. Our results suggest that scarred healing tendon cells respond to proinflammatory cytokines by promoting an imbalance in anabolic and catabolic functions, and that the heightened response involves p38 MAPK signaling activity. In contrast, embryonic cell responses are smaller in magnitude. These intriguing findings support a potential role for tendon cells in determining scarless versus scarred healing outcomes by regulating the balance between anabolic and catabolic functions during tendon healing.
成人的肌腱会作为瘢痕组织进行愈合，而胚胎的肌腱则通过未知的机制实现无瘢痕愈合。有瘢痕的肌腱愈合是由炎症驱动的合成代谢和分解代谢功能失衡引起的。为了测试无瘢痕与有瘢痕的年龄肌腱细胞对炎症条件的反应，我们用白细胞介素（IL）-1β处理胚胎和出生后肌腱细胞，并对胶原蛋白、基质金属蛋白酶（MMPs）、炎症介质和信号分子的磷酸化进行特征描述。在基线水平，出生后细胞表达的炎症介质水平明显更高。用 IL-1β处理后，出生后和胚胎细胞均上调了炎症介质和 MMPs。值得注意的是，出生后细胞分泌的炎症因子浓度高达胚胎培养物的 12.5 倍。IL-1β激活了两种细胞类型中的 NF-κB p65 和丝裂原激活蛋白激酶（MAPK）p38 途径，但出生后细胞中磷酸化的 p38 MAPK 水平比胚胎细胞高两倍。我们的结果表明，有瘢痕愈合的肌腱细胞通过促进合成代谢和分解代谢功能的失衡来响应促炎细胞因子，并且这种增强的反应涉及 p38 MAPK 信号活性。相比之下，胚胎细胞的反应幅度较小。这些有趣的发现支持肌腱细胞通过在肌腱愈合过程中调节合成代谢和分解代谢功能之间的平衡，在决定无瘢痕与有瘢痕愈合结果方面发挥潜在作用。
