Abstract
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.
Highlights
The mitochondria of tenocytes and Umbilical cord-mesenchymal stem cells (UC-MSCs) were stained with MitoTracker Green and CMXRos red fluorescent dyes for endogenous and exogenous mitochondrial detection, respectively
This study showed that intact exogenous mitochondrial transplantation could have protective effects against tumor necrosis factor-α (TNF-α)-induced damage in tenocytes and a collagenase-induced animal model of tendinopathy
This study provides the first evidence for the therapeutic effects of mitochondrial transfer in tendinopathy
Summary
Tendinopathies are common musculoskeletal problems associated with aging and sports [1]. Lateral elbow, Achilles, and patellar tendons are commonly affected areas [2]. Patients with tendinopathies suffer from activity-related pain and dysfunction [3]. There are conflicting results regarding the efficacies of conventional treatments for tendinopathies, such as physical modalities, corticosteroid injection, and analgesic medications [4,5]. The surgical repair of ruptured tendons has not been satisfying, especially in the elderly population [6]. The pathogenesis of tendinopathy involves interactions between processes related to degeneration and inflammation [7,8]. Inflammation is reportedly involved in the full spectrum of tendinopathies [9].
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