State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Int J Med Sci. 2023 Aug 6;20(9):1202-1211. doi: 10.7150/ijms.82925. eCollection 2023.
Skeletal muscle injuries are commonly observed during sports and trauma. Regular exercise promotes muscle repair; however, the underlying mechanisms require further investigation. In addition to exercise, osteopontin (OPN) contributes to skeletal muscle regeneration and fibrosis following injury. However, whether and how OPN affects matrix proteins to promote post-injury muscle repair remains uncertain. We recruited regular exercise (RE) and sedentary control (SC) groups to determine plasma OPN levels. Additionally, we developed a murine model of muscle contusion injury and compared the extent of damage, inflammatory state, and regeneration-related proteins in OPN knockout (OPN KO) and wild-type (WT) mice. Our results show that regular exercise induced the increase of OPN, matrix metalloproteinases (MMPs), and transforming growth factor-β (TGF-β) expression in plasma. Injured muscle fibers were repaired more slowly in OPN-KO mice than in WT mice. The expression levels of genes and proteins related to muscle regeneration were lower in OPN-KO mice after injury. OPN also promotes fibroblast proliferation, differentiation, and migration. Additionally, OPN upregulates MMP expression by activating TGF-β, which promotes muscle repair. OPN can improve post-injury muscle repair by activating MMPs and TGF-β pathways. It is upregulated by regular exercise. Our study provides a potential target for the treatment of muscle injuries and explains why regular physical exercise is beneficial for muscle repair.
骨骼肌损伤在运动和创伤中很常见。经常运动可促进肌肉修复；然而，其潜在机制仍需进一步研究。除运动外，骨桥蛋白（OPN）也有助于损伤后骨骼肌的再生和纤维化。然而，OPN 是否以及如何影响基质蛋白来促进损伤后肌肉修复尚不清楚。我们招募了经常运动（RE）和久坐不动的对照组（SC）来确定血浆 OPN 水平。此外，我们建立了肌肉挫伤损伤的小鼠模型，并比较了 OPN 敲除（OPN KO）和野生型（WT）小鼠的损伤程度、炎症状态和与再生相关的蛋白。我们的结果表明，经常运动诱导血浆中 OPN、基质金属蛋白酶（MMPs）和转化生长因子-β（TGF-β）表达增加。与 WT 小鼠相比，OPN-KO 小鼠的损伤肌肉纤维修复速度较慢。损伤后，OPN-KO 小鼠与肌肉再生相关的基因和蛋白表达水平较低。OPN 还通过激活 TGF-β促进成纤维细胞增殖、分化和迁移。此外，OPN 通过上调 MMP 表达来激活 TGF-β，从而促进肌肉修复。OPN 可通过激活 MMP 和 TGF-β 途径改善损伤后肌肉修复。它是由经常运动上调的。我们的研究为肌肉损伤的治疗提供了一个潜在的靶点，并解释了为什么经常进行体育锻炼有益于肌肉修复。
