Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy—A Target for Intervention

Abstract

Both acute and chronic tendon injuries are disabling sports medicine problems with no effective treatment at present. Sustained oxidative stress has been suggested as the major factor contributing to fibrosis and adhesion after acute tendon injury as well as pathological changes of degenerative tendinopathy. Numerous in vitro and in vivo studies have shown that the inhibition of oxidative stress can promote the tenogenic differentiation of tendon stem/progenitor cells, reduce tissue fibrosis and augment tendon repair. This review aims to systematically review the literature and summarize the clinical and pre-clinical evidence about the potential relationship of oxidative stress and tendon disorders. The literature in PubMed was searched using appropriate keywords. A total of 81 original pre-clinical and clinical articles directly related to the effects of oxidative stress and the activators or inhibitors of oxidative stress on the tendon were reviewed and included in this review article. The potential sources and mechanisms of oxidative stress in these debilitating tendon disorders is summarized. The anti-oxidative therapies that have been examined in the clinical and pre-clinical settings to reduce tendon fibrosis and adhesion or promote healing in tendinopathy are reviewed. The future research direction is also discussed.

Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

“…Moreover, SHED‐Exo treatment also enhanced the mRNA expression of antioxidant‐associated genes including superoxide dismutase 1 ( Sod1 ), catalase ( Cat ), and glutathione peroxidase ( Gpx1 ), which have been shown to influence stem cell senescence and induce tendinopathy progression (Figure 1m). [ 13 ]…”

“…Moreover, SHED-Exo treatment also enhanced the mRNA expression of antioxidant-associated genes including superoxide dismutase 1 (Sod1), catalase (Cat), and glutathione peroxidase (Gpx1), which have been shown to influence stem cell senescence and induce tendinopathy progression (Figure 1m). [13] TSPC senescence is frequently accompanied by a biased differentiation direction, as reflected by the declination of tenogenic differentiation, and enhancement of chondrogenic and osteogenic differentiation. [1] In this study, SHED-Exo bionanoparticles reversed the declined tenogenic differentiation of the AT-SCs, as evidenced by the enhanced collagen deposition and the increased expression of tenogenesis-related markers collagen type I (COL1) and fibromodulin (FMOD) (Figure 2a,b).…”

An Extracellular Vesicle-Cloaked Multifaceted Biocatalyst for Ultrasound-Augmented Tendon Matrix Reconstruction and Immune Microenvironment Regulation

“…4 In the initial stage, clinical and experimental studies proved that the level of reactive oxygen species (ROS) constantly increased in acutely injured tendons. 5,6 The accumulated ROS can result in tenocyte apoptosis, collagen degradation, suppressed tenogenesis, and M1 macrophage (M1φ) polarization. 7−9 The M1φ is a main driver of inflammation and the predominant Mφ phenotype at the onset of tendon injury responsible for secretion of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and further generation of ROS, which exacerbates the inflammatory cycle 10 and promotes a proinflammatory immune microenvironment.…”

“…13 Furthermore, the ROS-triggered oxidative stress impairment and inflammation can increase the COLIII/COLI ratio to produce tendon adhesion and fibrosis. 5 COLIII has a smaller diameter and more irregular alignment than that of COLI, which leads to decreased biomechanical strength. 14 Although COLIII could be replaced by COLI in the remodeling stage, 15 this process can take up to 12 months.…”

Energy‐Supporting Enzyme‐Mimic Nanoscaffold Facilitates Tendon Regeneration Based on a Mitochondrial Protection and Microenvironment Remodeling Strategy

“…[ 18 ] Reactive oxygen species (ROS), as a byproduct of oxidative phosphorylation, is a key signaling molecule regulating the biological activity of tenocytes. [ 19 ] Recent clinical studies reported that elevated levels of superoxide‐induced oxidative stress were associated with recurrent tears post‐arthroscopic rotator cuff repair. [ 20 ] Meanwhile, excessive ROS also promotes macrophage M1 polarization in the early stage of tendon repair, expands the inflammatory response, and exacerbates the vicious cycle of imbalanced immune microenvironment‐abnormal tendon repair.…”