Hydrogen peroxide induced tendinopathic changes in a rat model of patellar tendon injury

Abstract

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 μM H O (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 μM but not 500 μM H O group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 μM H O group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 μM H O group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H O impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H O -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

High cholesterol inhibits tendon‐related gene expressions in tendon‐derived stem cells through reactive oxygen species‐activated nuclear factor‐κB signaling

“…Several studies have also revealed that oxidative stress involved in the pathogenesis of tendinopathy. They found that H 2 O 2 attributed to tendinopathic changes in patellar tendon injury (Fu et al, 2018) and that tenocytes were particularly vulnerable to pro-oxidants like fluoroquinolones (Pouzaud, 2003) Therefore, p65 is liberated, translocates into the nucleus, and further activates target genes (Tornatore, Thotakura, Bennett, Moretti, & Franzoso, 2012). In this study, we first time reported that cholesterol-induced ROS activated the phosphorylation of IκBα and p-65 in TDSCs and in Achilles tendons of hypercholesterolemic mice.…”

“…Several studies have also revealed that oxidative stress involved in the pathogenesis of tendinopathy. They found that H 2 O 2 attributed to tendinopathic changes in patellar tendon injury (Fu et al, 2018) and that tenocytes were particularly vulnerable to pro-oxidants like fluoroquinolones (Pouzaud, 2003) (2016) have determined that NF-κB signaling pathway is one of the most highly induced pathways in tendon fibroblasts treated by platelet-rich plasma. As the transcription factor expressed in various cells, NF-κB-p65 remains inactive in the cytoplasm as a complex with IκB in resting cells.…”

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet

“…Cellular reduction-oxidation balance plays a crucial role in the homeostasis of connective tissues such as enthesis and tendon (Bestwick and Maffulli, 2004). Recent evidences suggest that oxidative stress plays a crucial role on tendinopathic changes (Lim et al, 2012;Lee et al, 2017;Fu et al, 2018). Morikawa et al (2014) reported that the antioxidant enzyme superoxide dismutase 1 deficiency in mice induced several histopathological changes in the supraspinatus tendon enthesis, including decreased type I collagen, formation of misaligned collagen fibers and misaligned 4-layered structure (tendon proper, FIGURE 8 | Proteins involved in the same interaction network regarding TF and TFO-HF group.…”

Estresse oxidativo e características ultrassonográficas do tendão anormal em jogadores de futebol de elite (um estudo piloto)

“…In comparison to controls receiving saline, the rat treated with H 2 O 2 showed impaired tendon healing and developed tendinopathic changes. 23 Guaraldo et al 24 submitted young and old rats to swimming exercise, and found an increased OS activity, which was more pronounced in old animals. Yuan et al, 25 exposing cultured human rotator cuff tendon fibroblasts to H 2 O 2 to create an in vitro OS situation, observed a pronounced apoptosis, via several pathways including the release of cytochrome-c from mitochondria to cytosol and the activation of caspase-3.…”

“…Em comparação com os controles que receberam soro fisiológico, os ratos tratados com H 2 O 2 apresentaram cicatrização do tendão prejudicada e desenvolveram alterações tendinopáticas. 23 Guaraldo et al 24 submeteram ratos jovens e velhos ao exercício de natação, e encontraram uma atividade de EO aumentada, e ainda mais acentuada em animais velhos. Yuan et al, 25 expondo fibroblastos do tendão do manguito rotador humano cultivados a H 2 O 2 para criar uma situação in vitro de EO, observaram apoptose pronunciada, através de várias vias, incluindo a liberação de citocromo-c de mitocôndrias a citosol e a ativação de caspase-3.…”