Aging Aggravates the Progression of Muscle Degeneration After Rotator Cuff Tears in Mice

Takada, Yasunari; Matsumura, Noboru; Shirasawa, Hideyuki; Yoda, Masaki; Matsumoto, Morio; Nakamura, Minoru; Horiuchi, Keisuke

doi:10.1016/j.arthro.2021.09.014

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…[ 55 ] Similarly, another study assessed the impact of aging on muscle degeneration following RCT in mice. [ 56 ] In the aged mice with RCT, there was a notable increase in fat tissue and muscular fibrosis, accompanied by elevated expression of adipogenic and fibrogenic markers compared to young mice. The findings suggest that aging plays a critical role in the development of muscular FI after RCT, and degeneration progresses over time in aged mice.…”

Section: Introductionmentioning

confidence: 99%

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

Wang,

Shen

et al. 2024

Advanced Biology

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Shoulder pain and disabilities are prevalent issues among the elderly population, with rotator cuff tear (RCT) being one of the leading causes. Although surgical treatment has shown some success, high postoperative retear rates remain a great challenge, particularly in elderly patients. Aging‐related degeneration of muscle, tendon, tendon‐to‐bone enthesis, and bone plays a critical role in the development and prognosis of RCT. Studies have demonstrated that aging worsens muscle atrophy and fatty infiltration, alters tendon structure and biomechanical properties, exacerbates enthesis degeneration, and reduces bone density. Although recent researches have contributed to understanding the pathophysiological mechanisms of aging‐related RCT, a comprehensive systematic review of this topic is still lacking. Therefore, this article aims to present a review of the pathophysiological changes and their clinical significance, as well as the molecular mechanisms underlying aging‐related RCT, with the goal of shedding light on new therapeutic approaches to reduce the occurrence of aging‐related RCT and improve postoperative prognosis in elderly patients.

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Section: Introductionmentioning

confidence: 99%

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

Wang,

Shen

et al. 2024

Advanced Biology

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“…On the other hand, RC disorders are often associated with degenerative changes in the RC muscles due to fatty infiltration and muscle atrophy (21,22). The presence of muscle degeneration affects the clinical practice of RC disorders (23).…”

Section: Introductionmentioning

confidence: 99%

More severe supraspinatus tendon degeneration on the contralateral shoulders in patients treated for symptomatic rotator cuff tears compared to healthy controls: a quantitative MRI-based study

Xie,

Li,

Chen

et al. 2024

Acta Radiol

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Background Patients treated for symptomatic rotator cuff tear (RCT) on one shoulder seem to have a higher prevalence of RCT on the contralateral shoulder. Purpose To compare the supraspinatus (SSP) tendon and RC muscle properties on the contralateral shoulder in patients after repair surgery to those healthy individuals using quantitative magnetic resonance imaging (MRI). Material and Methods A total of 23 patients treated for RCT (group A) and 23 healthy controls (group B) were recruited. Constant score, visual analog scale score (VAS), and MRI examinations were conducted. The SSP tendon structural status was graded based on the Zlatkin classification and quantified on ultrashort echo time (UTE)-T2* mapping images. Fatty degeneration of RC muscles was classified according to the Goutallier classification and quantified on T2 mapping. Results The Constant and VAS scores were comparable between groups A and B (all P >0.05). No significant differences were observed in tendon structural status between the two groups ( P >0.05). However, significant differences were established in UTE-T2* values of the SSP tendon on the distal subregion between groups A and B (16.4 ± 2.4 ms vs. 14.8 ± 1.2 ms; P = 0.01). Regarding muscle degeneration, no significant differences were displayed in T2 values and Goutallier classification of RC muscles (all P >0.05). Conclusion Patients with a treated RCT demonstrated inferior SSP tendon in the distal subregion on the contralateral shoulders one year postoperatively compared to that of healthy controls based on quantitative MRI data.

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Age‐dependent decline of B3AR agonist‐mediated activation of FAP UCP‐1 expression in murine models of chronic rotator cuff repair

Diaz,

Sang,

Garcia

et al. 2024

Journal Orthopaedic Research

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Amibegron, a β3‐adrenergic receptor (B3AR) agonist, has recently been shown to provide therapeutic effects for chronic rotator cuff (RC) tears by inducing the expression of uncoupling protein 1 (UCP‐1), a marker of brown fat, in fibroadipogenic progenitors (FAPs). However, it remains to be seen if these beneficial effects hold true with age and in older, more clinically relevant populations. This study seeks to understand the impacts of aging on the efficacy of amibegron to treat chronic RC tears. Young (4‐month‐old) and aged (33‐month‐old) C57BL/6 mice underwent a RC injury procedure with delayed repair (DR). Mice were equally randomized to receive amibegron or dimethyl sulfoxide (DMSO) treatments after repair. Functional ability was measured at baseline and 6‐weeks after DR. Wet muscle weight and histology of injured and contralateral supraspinatus were also analyzed 6‐weeks post‐DR. For in vitro histology and real‐time quantitative PCR experiments, FAPs were isolated from young and aged mice via fluorescence‐activated cell sorting. Young and aged FAPs were treated with amibegron or DMSO either immediately after seeding (early exposure) or 8‐days after seeding (late exposure). In vitro results showed that amibegron‐mediated FAP UCP‐1 expression decreases with age. In vivo data demonstrated that aged mice have a decreased responsiveness to amibegron and decreased propensity for intramuscular FAP UCP‐1 expression. Further, delayed amibegron treatment with RC repair did not lead to improvements in muscle atrophy and functional outcomes. Our findings demonstrate that age and the timing of interventions play a critical role in FAP‐targeted therapeutics for chronic injuries.

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Aging Aggravates the Progression of Muscle Degeneration After Rotator Cuff Tears in Mice

Cited by 4 publications

References 42 publications

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

More severe supraspinatus tendon degeneration on the contralateral shoulders in patients treated for symptomatic rotator cuff tears compared to healthy controls: a quantitative MRI-based study

Age‐dependent decline of B3AR agonist‐mediated activation of FAP UCP‐1 expression in murine models of chronic rotator cuff repair

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