Lee Ji Min, Hwang Jung Wook, Kim Mi Jin, Jung Sang Youn, Kim Kyung-Soo, Ahn Eun Hee, Min Kyunghoon, Choi Yong-Soo
Department of Biotechnology, CHA University, Seongnam 13488, Korea.
Division of Rheumatology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea.
Antioxidants (Basel). 2021 Apr 28;10(5):696. doi: 10.3390/antiox10050696.
Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.
肌腱病是一种常见的肌肉骨骼疾病，会导致疼痛和功能障碍。肌腱病的传统治疗方法和外科手术并不充分；因此，最近的研究集中在肌腱愈合的再生方法上。肌腱损伤通常发生在缺氧的关键区域，其特征是氧化应激增加和线粒体功能障碍；因此，外源性完整的线粒体可能具有治疗作用。我们旨在评估线粒体移植是否能诱导抗炎活性并调节肌腱病模型的代谢状态。通过离心成功地将外源性线粒体递送至受损的肌腱细胞中。受损肌腱细胞中的腱调蛋白和I型胶原蛋白水平得以恢复，同时核因子κB和基质金属蛋白酶1水平降低。线粒体移植减轻了氧化应激和线粒体膜电位的失调。诸如裂变蛋白1和动力相关蛋白1等激活的线粒体分裂标记物呈剂量依赖性下调。凋亡信号通路蛋白恢复到损伤前水平。在胶原酶注射诱导的大鼠肌腱病模型中也观察到了类似的变化。融入跟腱的外源性线粒体降低了炎症和分裂标记物水平。值得注意的是，胶原蛋白的产生得以恢复。我们的结果证明了直接线粒体移植对肌腱病的治疗效果。这些效果可能是通过线粒体动力学变化引起的抗炎和凋亡过程改变来解释的。
