Time‐course study of macrophage infiltration and inflammation in cast immobilization–induced atrophied muscle of mice

Kawanishi, Noriaki; Funakoshi, Tomoko; Machida, Shuichi

doi:10.1002/mus.26061

Cited by 20 publications

(22 citation statements)

References 24 publications

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“…This point was in agreement with some previous literature (28,29). Lengthy immobilization due to severe trauma, unwillingness, or pain caused muscle atrophy and capsular contracture (30).…”

Section: Discussionsupporting

confidence: 93%

Risk Factors for the Occurrence and Progression of Posttraumatic Elbow Stiffness: A Case-Control Study of 688 Cases

Qian

Shi

et al. 2020

Front. Med.

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Background: Elbow stiffness is a severe complication after trauma. Surgical or conservative treatments may be ineffective for restoring functional elbow motion. We aim to evaluate intrinsic and extrinsic factors for the occurrence and severity of elbow stiffness.Methods: This retrospective case–control study included mild/moderate stiffness, severe stiffness, and non-stiffness groups between January 2011 and December 2017 at a single orthopedic center. Multivariable logistic regression analysis and subgroup analysis were used to evaluate age, gender, body mass index, muscle strength, fracture type and site, injury mechanism, immobilization time, elbow dysfunction time, multiple surgeries, nerve symptoms, physical therapy, smoking and alcohol abuse, and dominant hand of stiff elbow as potential risk factors for the occurrence and severity of elbow stiffness.Results: There were 461 patients in the stiffness group and 227 patients in the non-stiffness group. The odds ratios (ORs) of the age, muscle strength, and injury mechanism were 0.960, 0.333, and 0.216 for the occurrence of elbow stiffness. In subgroup evaluation, increased cast immobilization time might be a risk factor for patients receiving conservative therapies (OR = 2.02; p = 0.014). In the evaluation on factors for progression of elbow stiffness, “multiple surgeries” might be a risk factor in surgical treatment by subgroup analysis (OR = 1.943; p = 0.026). Nevertheless, alcohol abuse might increase severity of elbow stiffness in conservatively treated patients (OR = 3.082; p = 0.025).Conclusion: Increased cast immobilization time in the conservative therapy might be a risk factor for stiffness occurrence. Multiple surgeries might be risk factors for stiffness progression. Alcohol abuse potentially increased stiffness severity after conservative treatment.

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“…This point was in agreement with some previous literature (28,29). Lengthy immobilization due to severe trauma, unwillingness, or pain caused muscle atrophy and capsular contracture (30).…”

Section: Discussionsupporting

confidence: 93%

Risk Factors for the Occurrence and Progression of Posttraumatic Elbow Stiffness: A Case-Control Study of 688 Cases

Qian

Shi

et al. 2020

Front. Med.

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“…Unexpectedly, we found that gene expression levels of atrophy-related genes were increased not only in Sol but also in EDL, and expression levels were higher in EDL than in Sol. MuRF1 and Atrogin-1 mRNA levels increased after 1 day of denervated, spinal cord-resected or cast-immobilized muscle, reached a peak at 3 days, and then decreased toward basal levels at 14 days (Sacheck et al 2007;Kawanishi et al 2018). Significant loss of muscle weight persisted until 14 days of disuse (Kawanishi et al 2018) and maximally decreased at 14-28 days (Sacheck et al 2007).…”

Section: Discussionmentioning

confidence: 96%

“…MuRF1 and Atrogin-1 mRNA levels increased after 1 day of denervated, spinal cord-resected or cast-immobilized muscle, reached a peak at 3 days, and then decreased toward basal levels at 14 days (Sacheck et al 2007;Kawanishi et al 2018). Significant loss of muscle weight persisted until 14 days of disuse (Kawanishi et al 2018) and maximally decreased at 14-28 days (Sacheck et al 2007). These findings indicated that, when actual muscle weight reduction occurred, there was no further upregulation of these genes.…”

Section: Discussionmentioning

confidence: 96%

One week, but not 12 hours, of cast immobilization alters promotor DNA methylation patterns in the nNOS gene in mouse skeletal muscle

Tobisawa

Ito

Sudo

et al. 2019

The Journal of Physiology

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Key points DNA methylation may play an important role in regulating gene expression in skeletal muscle to adapt to physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) in skeletal muscle is a key regulator of skeletal muscle mass; however, it is unclear whether nNOS expression is regulated by DNA methylation. We found that 1 week of cast immobilization increased nNOS DNA methylation levels and downregulated nNOS gene expression in atrophic slow‐twitch soleus muscle from the mouse leg. These changes were not detected in non‐atrophic fast‐twitch extensor digitorum longus muscle. Twelve hours of cast immobilization decreased nNOS gene expression, whereas nNOS DNA methylation levels were unchanged, suggesting that downregulation of nNOS gene expression by short‐term muscle inactivity is independent of the DNA methylation pattern. These findings contribute to a better understanding of the maintenance of skeletal muscle mass and prevention of muscle atrophy by epigenetic mechanisms via the nNOS/NO pathway. Abstract DNA methylation is a mechanism that controls gene expression in skeletal muscle under various environmental stimuli, such as physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) regulates muscle atrophy in skeletal muscle. However, the mechanisms regulating nNOS expression in atrophic muscle remain unclear. We hypothesized that nNOS expression in atrophic muscle is regulated by DNA methylation of the nNOS promotor in soleus (Sol; slow‐twitch fibre dominant) and extensor digitorum longus (EDL; fast‐twitch fibre dominant) muscles. One week of cast immobilization induced significant muscle atrophy in Sol but not in EDL. We showed that 1 week of cast immobilization increased nNOS DNA methylation levels in Sol, although only a minor change was detected in EDL. Consistent with the increased DNA methylation levels in atrophic Sol, the gene expression levels of total nNOS and nNOSµ (i.e. the major splicing variant of nNOS in skeletal muscle) decreased. The abundance of the nNOS protein and cell membrane (especially type IIa fibre) immunoreactivity also decreased in atrophic Sol. These changes were not observed in EDL after 1 week of cast immobilization. Furthermore, despite the lack of significant atrophy, 12 h of cast immobilization decreased gene expression levels of total nNOS and nNOSµ in Sol. However, no association was detected between nNOS DNA methylation and gene expression. The expression of the nNOSβ gene, another splicing variant of nNOS, in EDL was unchanged by cast immobilization, whereas its expression was not detected in Sol. We concluded that chronic adaptation of nNOS gene expression in cast immobilized muscle may involve nNOS DNA methylation.

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“…The mechanism for the increase in FOXO3A expression is currently unclear. However, under catabolic states such as immobilization, FOXO3A expression is known to increase in skeletal muscle (Okamoto and Machida, ; Kawanishi et al, ). Considering these facts, FOXO3A is possibly involved in the bluntation of the muscle‐hypertrophic effect observed in the group with excessive shortening of the recovery period; thus, the involvement of FOXO proteins in the acceleration of protein ubiquitination, ubiquitin ligase mRNA expression, and autophagosome formation should be clarified in future investigations.…”

Section: Discussionmentioning

confidence: 99%

Influence of shortened recovery between resistance exercise sessions on muscle‐hypertrophic effect in rat skeletal muscle

et al. 2019

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Resistance exercise training induces muscle hypertrophy, and recovery between sessions is one of the major determinants of this effect. However, the effect of the recovery period between sessions on muscle hypertrophy following resistance exercise training remains unclear. To elucidate the effect of recovery period on hypertrophy, in the present study, we investigated changes in protein degradation systems and hypertrophic responses in rat skeletal muscle to resistance training with variable recovery periods. In the conventional recovery group (exercised every 72 h) and a shorter recovery group (exercised every 24 h), 18 bouts of resistance exercise consisting of 50 repetitions of a 3‐sec maximal isometric contraction caused muscle hypertrophy and slight activation of muscle protein degradation systems. By contrast, in an excessively shorter recovery group (exercised every 8 h), 18 bouts of resistance exercise did not cause hypertrophy and markedly activated protein degradation systems, accompanied by inflammatory responses. These observations indicate that excessive shortening of recovery between sessions does not cause skeletal muscle hypertrophy, likely due to the activation of proteolysis induced by inflammatory responses to resistance exercise training.

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Time‐course study of macrophage infiltration and inflammation in cast immobilization–induced atrophied muscle of mice

Cited by 20 publications

References 24 publications

Risk Factors for the Occurrence and Progression of Posttraumatic Elbow Stiffness: A Case-Control Study of 688 Cases

Risk Factors for the Occurrence and Progression of Posttraumatic Elbow Stiffness: A Case-Control Study of 688 Cases

One week, but not 12 hours, of cast immobilization alters promotor DNA methylation patterns in the nNOS gene in mouse skeletal muscle

Influence of shortened recovery between resistance exercise sessions on muscle‐hypertrophic effect in rat skeletal muscle

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