Mitochondrial dysfunction and potential mitochondrial protectant treatments in tendinopathy

Abstract

Tendinopathy is a common musculoskeletal condition that affects a wide range of patients, including athletes, laborers, and older patients. Tendinopathy is often characterized by pain, swelling, and impaired performance and function. The etiology of tendinopathy is multifactorial, including both intrinsic and extrinsic mechanisms. Various treatment strategies have been described, but outcomes are often variable, as tendons have poor intrinsic healing potential compared with other tissues. Therefore, several novel targets for tendon regeneration have been identified and are being explored. Mitochondria are organelles that generate adenosine triphosphate, and they are considered to be the power generators of the cell. Recently, mitochondrial dysfunction verified by increased reactive oxygen species (ROS), decreased superoxide dismutase activity, cristae disorganization, and decreased number of mitochondria has been identified as a mechanism that may contribute to tendinopathy. This has provided new insights for studying tendinopathy pathogenesis and potential treatments via antioxidant, metabolic modulation, or ROS inhibition. In this review, we present the current understanding of mitochondrial dysfunction in tendinopathy. The review summarizes the potential mechanism by which mitochondrial dysfunction contributes to the development of tendinopathy, as well as the potential therapeutic benefits of mitochondrial protectants in the treatment of tendinopathy.

A Biomaterial‐Based Hedging Immune Strategy for Scarless Tendon Healing

“…[ 30 ] Normal cell proliferation is promoted by hyperactive mitochondria under material‐ and energy‐sufficient conditions. [ 31 ] As assayed by the mitochondrial fluorescence probe, the mitochondrial density in the Him‐MFM group were the highest. Correspondingly, the ATP/ADP level was 1.55 ± 0.07 in the Him‐MFM group, which was also higher than those of 1.07 ± 0.02, 1.13 ± 0.04, 1.02 ± 0.05, and 0.99 ± 0.06 in the other groups.…”

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

“…The transition from limited ATP synthesis to ROS production leads to oxidative damage to mitochondria and other organelles, which could convert TDSCs to a pro‐inflammatory state, thereby initiating the senescence program. [ 43 , 44 ] Moreover, severe oxidative stress could lead to apoptosis of tenocytes, which is mediated by mitochondrial release of cytochrome C and triggering caspase‐3 activation. [ 45 ] As the main pro‐inflammatory cytokines in SASP, the expression of IL‐1 β , IL‐6, TNF‐ α , and IFN‐ γ was down‐regulated in H 2 O 2 + CeNPs group, demonstrating a remission of the inflammatory state of the TDSCs (Figure 6B–E ).…”

“…Pathologically, oxidative stress mediates inflammatory activation, including activation of M1 macrophages and unrestricted secretion of pro‐inflammatory factors. [ 43 , 54 ] Meanwhile, M1 macrophage polarization and persistent inflammation initiate senescence programs. [ 44 , 55 ] And SASPs, including IL‐1 α , IL‐6, and IFN‐ γ could induce M1 polarization of macrophages, thereby enhancing the early inflammatory response.…”

SS-31 as a Mitochondrial Protectant in the Treatment of Tendinopathy

“…T he pathogenesis of tendinopathy is multifactorial and complex, and current treatment strategies are associated with variable efficacy and a high rate of recurrent symptoms, possibly owing to the poor regenerative potential of tendon and incomplete characterization of the underlying pathophysiology 1,33 . Our recent studies have revealed the role of mitochondrial dysfunction in the onset and progression of tendinopathy 3,6 . Thus, agents that target mitochondria may represent an effective strategy for treatment of tendinopathy.…”

“…Mitochondria are the powerhouses of cells and play fundamental roles in basic development and repair processes 3,4 . Mitochondrial dysfunction has been found to influence tendon healing following rotator cuff injury 5 .…”