Effect of Fatty Acid–Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis

Lee, Yong-Soo; Kim, Ja-Yeon; Kim, Kwang Il; Ki, Se‐Young; Chung, Seok Won

doi:10.1177/0363546519873856

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…In this study, fatty infiltration was determined based on the content FABP4 protein levels in the SS and DT muscles, which we found were comparable between the 2 muscles. This in contrast to a recent study by Lee et al, 25 which used a different and semiquantitative technique to assess FABP4 and demonstrated lower FABP4 levels, representative of the absence of fatty infiltration, in the DT muscle compared with the SS muscle. 25 These findings are in favor of the use of DT as a reference muscle.…”

Section: Discussioncontrasting

confidence: 99%

Supraspinatus and deltoid muscle fiber composition in rotator cuff tear conditions

Ravn¹,

Ostergaard²,

Schroeder³

et al. 2020

JSES International

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Background Rotator cuff (RC) tears are associated with RC muscle atrophy and changes in composition that are crucial to the prognosis of RC repair. The aim of this study was to characterize muscle fiber composition in the supraspinatus (SS) muscle under tear conditions. Methods Muscle biopsies were obtained from 21 patients undergoing surgery for an RC tendon tear. Biopsies were obtained from the musculotendinous junction of the SS muscle, and control biopsies were harvested from the deltoid muscle (DT). Biopsies were immunohistochemically processed for detection of type 1 (slow type) and type 2 (fast type) fibers and analyzed using unbiased, stereological principles. We counted the total numbers of type 1 and 2 muscle fibers/mm 2 , and fiber diameter was used to estimate muscle fiber atrophy and hypertrophy. Results We found significantly more type 2 cells/mm 2 in the SS compared with the DT ( P < .01). In addition, we found a significantly higher fraction of type 1 fibers than type 2 fibers in the DT ( P < .01), whereas both fiber types were equally present in the SS. The diameters of SS cells were generally smaller than those of DT cells. Atrophy of especially SS type 2 fibers was also demonstrated. Fiber atrophy was more pronounced in men than women. Conclusion The changes in the composition of SS muscle cell types suggest a shift from type 1 to type 2 muscle fibers and atrophy of both type 1 and 2 fibers. This composition indicates loss of endurance and rapid fatigue of the SS muscle under RC tear conditions.

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Section: Discussioncontrasting

confidence: 99%

Supraspinatus and deltoid muscle fiber composition in rotator cuff tear conditions

Ravn¹,

Ostergaard²,

Schroeder³

et al. 2020

JSES International

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 96%

Supraspinatus and deltoid muscle fiber diversity in rotator cuff tear conditions

Ravn

Ostergaard

Schroeder

et al. 2019

Preprint

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Background: Rotator cuff (RC) tears are associated with RC muscle atrophy and changes in composition that are crucial to the prognosis of RC repair. The aim of this study was to characterize muscle fiber composition in the supraspinatus (SS) muscle under tear conditions. Methods: Muscle biopsies were obtained from 21 patients undergoing surgery for RC tendon tear. Biopsies were obtained from the musculotendinous junction of the SS muscle and control biopsies were harvested from the deltoid muscle (DT). Biopsies were immunohistochemically processed for detection of type 1 (slow type) and type 2 (fast type) fibers and analyzed using unbiased, stereological principles. We counted the total numbers of type 1 and 2 muscle fibers/mm 2 and fiber diameter was used to estimate muscle fiber atrophy and hypertrophy. Results: We found significantly more type 2 cells/mm 2 in the SS compared to the DT (p<0.01). In addition, we found a significantly higher fraction of type 1 fibers than type 2 fibers in the DT (p<0.01), whereas both fiber types were equally present in the SS. The diameters of SS cells were generally smaller than those of DT cells. Atrophy of especially SS type 2 fibers was also demonstrated. Fiber atrophy was more pronounced in men than women. Discussion: The changes in the composition of SS muscle cell types suggest a shift from type 1 to type 2 muscle fibers and atrophy of both type 1 and 2 fibers. This composition indicates loss of endurance and rapid fatigue of the SS muscle under RC tear conditions.

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“…However, given that the rapamycin derivates are clinically used as antitumor agents and exhibit various systemic side effects, the use of rapamycin to treat patients with RCT will not be clinically acceptable. Lee et al 11,12 showed that the expression of FABP4, a protein involved in fatty acid metabolism, is upregulated in patients with RCT and that targeting of FABP4 reduces fatty degeneration in a rat model. While this strategy may deserve further investigations, FABP4 inhibitors are not currently used clinically, and the potential adverse effects are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice

et al. 2021

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Background: The infiltration of fat tissue into skeletal muscle, a condition referred to as muscle fatty infiltration or fatty degeneration, is regarded as an irreversible event that significantly compromises the motor function of skeletal muscle. Purpose: To investigate the effect of retinoic acid receptor (RAR) agonists in suppressing the adipogenic differentiation of fibroadipogenic progenitors (FAPs) in vitro and fatty infiltration after rotator cuff tear in mice. Study Design: Controlled laboratory study. Methods: FAPs isolated from mouse skeletal muscle were cultured in adipogenic differentiation medium in the presence or absence of an RAR agonist. At the end of cell culture, adipogenic differentiation was evaluated by gene expression analysis and oil red O staining. A mouse model of fatty infiltration—which includes the resection of the rotator cuff, removal of the humeral head, and denervation the supraspinatus muscle—was used to induce fatty infiltration in the supraspinatus muscle. The mice were orally or intramuscularly administered with an RAR agonist after the surgery. Muscle fatty infiltration was evaluated by histology and gene expression analysis. Results: RAR agonists effectively inhibited the adipogenic differentiation of FAPs in vitro. Oral and intramuscular administration of RAR agonists suppressed the development of muscle fatty infiltration in the mice after rotator cuff tear. In accordance, we found a significant decrease in the number of intramuscular fat cells and suppressed expression in adipogenic markers. RAR agonists also increased the expression of the transcripts for collagens; however, an accumulation of collagenous tissues was not histologically evident in the present model. Conclusion: Muscle fatty infiltration can be alleviated by RAR agonists through suppressing the adipogenic differentiation of FAPs. The results also suggest that RAR agonists are potential therapeutic agents for treating patients who are at risk of developing muscle fatty infiltration. The consequence of the increased expression of collagen transcripts by RAR agonists needs to be clarified. Clinical Relevance: RAR agonists can be used to prevent the development of muscle fatty infiltration after rotator cuff tear. Nevertheless, further studies are mandatory in a large animal model to examine the safety and efficacy of intramuscular injection of RAR agonists.

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Effect of Fatty Acid–Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis

Cited by 16 publications

References 42 publications

Supraspinatus and deltoid muscle fiber composition in rotator cuff tear conditions

Supraspinatus and deltoid muscle fiber composition in rotator cuff tear conditions

Supraspinatus and deltoid muscle fiber diversity in rotator cuff tear conditions

Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice

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