Chronic Muscle Injury Research Articles

Ultrasound-Guided Percutaneous Needle Electrolysis in Dancers with Chronic Soleus Injury: A Randomized Clinical Trial.

Damage to intramuscular tendons is very common in sports injuries, specifically in soleus muscle injuries. This study sought to compare the effects of applying ultrasound- (US-) guided percutaneous needle electrolysis (PNE) in combination with an eccentric exercise program on pain and functionality in dancers with chronic soleus injury, located in the central tendon. Thirty dancers with injured central tendon of the soleus muscle were randomly allocated to a PNE group (n = 10), an eccentric exercise group (n = 10), or a combined group (n = 10). Pain, ankle dorsiflexion range of motion (DROM), endurance, the heel raise test, the DFOS questionnaire, and the minimal clinically important difference (MCID) were analyzed at baseline and after treatment (four weeks). Over half (52%) of the dancers had a chronic soleus muscle injury. Variables for pain, DROM, the heel rise test, ADL, technique, DFOS total, and DFOS-subjective variables showed significant differences (P < 0.05) in pretreatment and posttreatment in all groups, whereas no significant differences were observed between intervention groups. However, the combined group showed a higher percentage of changes compared to the other groups, and these dancers had greater perceived changes (MCID = 4.70 ± 1.42). The conclusion of the study was that dancers with chronic soleus injury, located in the central tendon, treated with a combination of US-guided PNE and an eccentric exercise program displayed improved outcomes compared to the application of PNE therapy or eccentric exercise alone. The US-guided PNE, combined with an eccentric exercise program, is a useful therapeutic tool for the treatment of chronic soleus injury, located in the central tendon. The trial is registered with NCT04042012.

Analysis of the effect of overusing thumbs on smartphone games.

ObjectiveTo assess the impact of repetitive movements of the thumb caused by playing a smartphone game continuously for 30 min.MethodsThis study recruited healthy volunteers. They were instructed to play a game called Subway Surfers, which ran continuously. Subjects played the game for 30 min. The function of the abductor pollicis brevis and extensor pollicis brevis muscles was assessed by surface electromyography and the signals were obtained at 10 min, 20 min and 30 min. The median frequency (MDF) was used as an indicator of muscle fatigue. A visual analogue scale (VAS) was used to assess the subjective discomfort of the volunteers.ResultsTwelve subjects participated in this study. The MDF of the abductor pollicis brevis and extensor pollicis brevis muscles decreased significantly over the test period. The MDF of the extensor pollicis brevis had decreased significantly by 10 min after the start of the gaming session, while the abductor pollicis brevis had decreased significantly by 20 min. The VAS scores significantly increased after 30 min of continuous gaming.ConclusionsThis study suggests that playing continuous games on a smartphone might result in chronic muscle injury. Continuous gaming time should be kept below 20 minutes.

Mineralocorticoid Receptor Signaling Contributes to Normal Muscle Repair After Acute Injury.

Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and muscle progenitor cells within the muscle microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic muscle injury, but eventually, the regenerative portion of the cycle is disrupted and fibrosis replaces degenerated muscle fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated to increase skeletal muscle function, decrease fibrosis, and directly improve membrane integrity in muscular dystrophy mice, and therefore are being tested clinically. Conditional knockout of MR from muscle fibers in muscular dystrophy mice also improves skeletal muscle function and decreases fibrosis. The mechanism of efficacy likely results from blocking MR signaling by its endogenous agonist aldosterone, being produced at high local levels in regions of muscle damage by infiltrating myeloid cells. Since chronic and acute injuries share the same cellular processes to regenerate muscle, and MR antagonists are clinically used for a wide variety of conditions, it is crucial to define the role of MR signaling in normal muscle repair after injury. In this study, we performed acute injuries using barium chloride injections into tibialis anterior muscles both in myofiber MR conditional knockout mice on a wild-type background (MRcko) and in MR antagonist-treated wild-type mice. Steps of the muscle regeneration response were analyzed at 1, 4, 7, or 14 days after injury. Presence of the aldosterone synthase enzyme was also assessed during the injury repair process. We show for the first time aldosterone synthase localization in infiltrating immune cells of normal skeletal muscle after acute injury. MRcko mice had an increased muscle area infiltrated by aldosterone synthase positive myeloid cells compared to control injured animals. Both MRcko and MR antagonist treatment stabilized damaged myofibers and increased collagen infiltration or compaction at 4 days post-injury. MR antagonist treatment also led to reduced myofiber size at 7 and 14 days post-injury. These data support that MR signaling contributes to the normal muscle repair process following acute injury. MR antagonist treatment delays muscle fiber growth, so temporary discontinuation of these drugs after a severe muscle injury could be considered.

Sustained elevation of MG53 in the bloodstream increases tissue regenerative capacity without compromising metabolic function

MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.

Platelet-Rich Fibrin and its Emerging Therapeutic Benefits for Musculoskeletal Injury Treatment.

New therapies that accelerate musculoskeletal tissue recovery are highly desirable. Platelet-rich fibrin (PRF) is a leukocyte- and platelet-rich fibrin biomaterial that acts as a binding site for both platelets and growth factors. Through increasing the local concentration of growth factors at specific tissues, PRF promotes tissue regeneration. PRF has been frequently used in combination with bone graft materials to reduce healing times and promote bone regeneration during maxillofacial surgery. However, its benefits during muscle repair and recovery are less well-documented. Here, we perform a narrative review on PRF therapies and muscle injuries to ascertain its beneficial effects. We reviewed the factors that contribute to the biological activity of PRF and the published pre-clinical and clinical evidence to support its emerging use in musculoskeletal therapy. We include in vitro studies, in vivo animal studies and clinical articles highlighting both the success and failures of PRF treatment. PRF can promote the healing process when used in a range of orthopaedic and sports-related injuries. These include cartilage repair, rotator cuff surgery and anterior cruciate ligament surgery. However, conflicting data for these benefits have been reported, most likely due to inconsistencies in both PRF preparation protocols and dosing regimens. Despite this, the literature generally supports the use of PRF as a beneficial adjuvant for a range of chronic muscle, tendon, bone or other soft tissue injuries. Further clinical trials to confirm these benefits require consistency in PRF preparation and the classification of a successful clinical outcome to fully harness its potential.

Angiotensin‐converting enzyme 2 deficiency accelerates and angiotensin 1‐7 restores age‐related muscle weakness in mice

BackgroundA pharmacologic strategy for age‐related muscle weakness is desired to improve mortality and disability in the elderly. Angiotensin‐converting enzyme 2 (ACE2) cleaves angiotensin II into angiotensin 1‐7, a peptide known to protect against acute and chronic skeletal muscle injury in rodents. Since physiological aging induces muscle weakness via mechanisms distinct from other muscle disorders, the role of ACE2‐angiotensin 1‐7 in age‐related muscle weakness remains undetermined. Here, we investigated whether deletion of ACE2 alters the development of muscle weakness by aging and whether angiotensin 1‐7 reverses muscle weakness in older mice.MethodsAfter periodic measurement of grip strength and running distance in male ACE2KO and wild‐type mice until 24 months of age, we infused angiotensin 1‐7 or vehicle for 4 weeks, and measured grip strength, and excised tissues. Tissues were also excised from younger (3‐month‐old) and middle‐aged (15‐month‐old) mice. Microarray analysis of RNA was performed using tibialis anterior (TA) muscles from middle‐aged mice, and some genes were further tested using RT‐PCR.ResultsGrip strength of ACE2KO mice was reduced at 6 months and was persistently lower than that of wild‐type mice (p < 0.01 at 6, 12, 18, and 24‐month‐old). Running distance of ACE2KO mice was shorter than that of wild‐type mice only at 24 months of age [371 ± 26 vs. 479 ± 24 (m), p < 0.01]. Angiotensin 1‐7 improved grip strength in both types of older mice, with larger effects observed in ACE2KO mice (% increase, 3.8 ± 1.5 and 13.3 ± 3.1 in wild type and ACE2KO mice, respectively). Older, but not middle‐aged ACE2KO mice had higher oxygen consumption assessed by a metabolic cage than age‐matched wild‐type mice. Angiotensin 1‐7 infusion modestly increased oxygen consumption in older mice. There was no difference in a wheel‐running activity or glucose tolerance between ACE2KO and wild‐type mice and between mice with vehicle and angiotensin 1‐7 infusion. Analysis of TA muscles revealed that p16INK4a, a senescence‐associated gene, and central nuclei of myofibers increased in middle‐aged, but not younger ACE2KO mice. p16INK4a and central nuclei increased in TA muscles of older wild‐type mice, but the differences between ACE2KO and wild‐type mice remained significant (p < 0.01). Angiotensin 1‐7 did not alter the expression of p16INK4a or central nuclei in TA muscles of both types of mice. Muscle ACE2 expression of wild‐type mice was the lowest at middle age (2.6 times lower than younger age, p < 0.05).ConclusionsDeletion of ACE2 induced the early manifestation of muscle weakness with signatures of muscle senescence. Angiotensin 1‐7 improved muscle function in older mice, supporting future application of the peptide or its analogues in the treatment of muscle weakness in the elderly population.

Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors

BackgroundChronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration.MethodsCell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration.ResultsWe identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear.ConclusionsThese findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.

Nutraceutical and Pharmaceutical Interventions Improve Fatigue Resistance in Dystrophic Skeletal Muscle

Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy (DMD), which is caused by the absence of functional dystrophin protein. Likewise, chronic muscle injuries are common in military personnel. We have previously shown PGC‐1α‐mediated protection of dystrophic muscle via gene transfer approaches, however, investigations using quercetin (Q) to activate the PGC‐1α pathway have been equivocal. Quercetin activates PGC‐1α through Sirtuin‐1, an NAD+‐dependent deacetylase, however, NAD+ may be depleted in dystrophic skeletal muscle. Therefore, the purpose of this investigation was to determine the extent to which supplementation with Q and nicotinamide riboside (NR), an NAD+ precursor, alone and in combination, improved function of dystrophic skeletal muscle. We hypothesized that the addition of Q or NR would improve diaphragm, soleus and extensor digitorum longus (EDL) muscle function, and when given in combination would cause synergistic effects. To address this hypothesis, muscle function from DBA (healthy), D2‐mdx (dystrophin deficient), and D2‐mdx mice fed Q (0.2% of diet), NR (400 mg/kg/d), and Q/NR was assessed. In addition, to mimic typical pharmacology of DMD patients an additional group was fed Q/NR and treated with prednisone (10 mg/L; Pred) and lisinopril (66 mg/L: Lis). Treatment was started at 4 mo of age under blinded conditions and ended upon tissue collection at 11 mo of age. Dystrophin deficiency impaired diaphragm specific tension and was not corrected by treatments, nor was fatigue resistance improved. In the EDL, dystrophin deficiency decreased resistance to contraction‐induced injury that was partially restored in the Q/NR/Lis/Pred group compared to untreated D2‐mdx. Specific tension in the EDL and soleus was decreased in dystrophic muscle and was not altered by treatments. Interestingly, Q, NR, and Q/NR increased soleus fatigue resistance through 1 min of a fatigue protocol compared to untreated dystrophic controls, but was similar thereafter (10 min). Fatigue resistance was increased throughout the fatigue protocol in the Q/NR/Lis/Pred group compared to D2‐mdx. This finding suggests that Q, NR or Q/NR may improve soleus glycolytic capacity resulting in sustained force production for the first minute of exercise and that the addition of Lis and Pred augments these effects. In total these data suggest that treatment with Q, NR, and Q/NR provide limited protection to dystrophic muscle that is enhanced by the addition of Lis/Pred. As many activities of daily living are completed within 1 min, increased fatigue resistance demonstrated herein, while modest, may decrease disease burden in DMD patients and in other chronic muscle injury conditions.Support or Funding InformationSupported by Parent Project Muscular Dystrophy, Ryan's Quest and Michael's Cause.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

P.320 - Osteopontin expression during chronic and acute muscle injury

P.320 - Osteopontin expression during chronic and acute muscle injury

Advanced MRI Techniques for Muscle Imaging.

AbstractAdvanced magnetic resonance imaging (MRI) techniques can evaluate a wide array of muscle pathologies including acute or chronic muscle injury, musculotendinous response to injury, intramuscular collections and soft tissue masses, and others. In recent years, MRI has played a more important role in muscle disease diagnosis and monitoring. MRI provides excellent spatial and contrast resolution and helps direct optimal sites for muscle biopsy. Whole-body MRI now helps identify signature patterns of muscular involvement in large anatomical regions with relative ease. Quantitative MRI has advanced the evaluation and disease tracking of muscle atrophy and fatty infiltration in entities such as muscular dystrophies. Multivoxel magnetic resonance spectroscopy (MRS) now allows a more thorough, complete evaluation of a muscle of interest without the inherent sampling bias of single-voxel MRS or biopsy. Diffusion MRI allows quantification of muscle inflammation and capillary perfusion as well as muscle fiber tracking.

Is Massage Therapy in Acute Cases Always Contraindicated?

Massage therapy always known to be beneficial in chronic muscle injury leading to adhesions. Therapeutic effect of massage helps in releasing tension, eliminates pain and allow normal range and movement of the part thereby improves blood circulation. Massage therapy following an injury is contraindicated. But can it be indicated in some muscle injuries? Can massage following a particular injury brings immediate effect? Have we misjudged and ignored the effectiveness of massage in mild acute cases?

The Treatment of Glucocorticoid Steroid Resistant Chronic Inflammatory Disease with Moxa Tar

Currently glucocorticoid steroid is the mainstay of treatment of chronic inflammatory diseases like asthma, COPD, rheumatoid arthritis. But many chronic inflammatory diseases are resistant to glucocorticoid steroid like pulmonary fibrosis, atherosclerosis related diseases, chronic laryngitis and chronic muscle injury. Glucocorticoid steroid has been thoroughly studied and its therapeutic potential has been exhausted, and therefore there is a need to develop new anti-inflammatory drugs or anti-inflammatory therapies. Moxa (Artemisia Argyi) is a plant, its burning smoke or Tar has strong anti-inflammatory property. In this article the author wants to introduce a new way (Moxa Tar) of treating glucocorticoid steroid resistant chronic inflammatory diseases based on some clinical experiments and hypothesis of the author’s personal observation. The purpose of this article is to open up a new field and raise researchers’ attention to this new field for developing new anti-inflammatory drugs or anti-inflammatory therapies. The methods used in this study are Crossover design, i.e. patients serve as their own control, comparing the clinical symptoms and signs before and after Moxa Tar treatment.

Toll-like receptor signalling in regenerative myogenesis: friend and foe

Skeletal muscle regeneration in normal and diseased muscle is regulated by multiple factors and cells present in the injured muscle micro-environment. In addition to muscle progenitor cells, several immunocytes participate in the regenerative response. Among them, macrophages are one of the most important components of the immune response that governs the step-wise progression of muscle regeneration. The initial role of macrophages is to phagocytose muscle cell debris and later, through their transition to an anti-inflammatory phenotype, they promote regeneration. However, in several genetic muscle disorders, continuous muscle injury disrupts the balance between pro-inflammatory and anti-inflammatory macrophages, leading to an overall inflammatory milieu and inhibition of muscle regeneration. Accumulating evidence suggests that Toll-like receptor (TLR)-mediated signalling plays an important role in the regulation of macrophage phenotypes during regenerative myogenesis in response to both acute and chronic muscle injury. Here, we discuss the role of TLR signalling in regulating macrophage phenotypes and skeletal muscle regeneration in healthy and diseased muscle. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chronic Paraspinal Muscle Injury Model in Rat.

ObjectiveThe objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat.MethodsFifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations.Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers.ConclusionOur chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles.

Numb is required to prevent p53-dependent senescence following skeletal muscle injury

Regeneration relies on coordinated action of multiple cell types to reconstitute the damaged tissue. Here we inactivate the endocytic adaptor protein Numb in skeletal muscle stem cells prior to chronic or severe muscle injury in mice. We observe two types of senescence in regenerating muscle; a transient senescence in non-myogenic cells of control and Numb mutant mice that partly depends on INK4a/ARF activity, and a persistent senescence in myogenic cells lacking Numb. The senescence levels of Numb-deficient muscle is reduced to wild type levels by an anti-oxidant treatment or p53 ablation, resulting in functional rescue of the regenerative potential in Numb mutants. Ex vivo experiments suggest that Numb-deficient senescent cells recruit macrophages to sustain inflammation and drive fibrosis, two hallmarks of the impaired muscle regeneration in Numb mutants. These findings provide insights into previously reported developmental and oncogenic senescence that are also differentially regulated by p53.

EXTRACORPOREAL SHOCKWAVE TERAPY TO TREAT CHRONIC MUSCLE INJURY.

ABSTRACTObjective: To evaluate the low energy extracorporeal shock waves therapy (ESWT) associated with physical therapy in the treatment of chronic muscle injuries classified as grades 2 and 3 in the lower limbs of amateur athletes. Methods: Eight athletes presenting with lower limb muscle injury for more than three weeks were treated with physiotherapy and ESWT. We evaluated the following parameters during treatment: palpable gap, muscle strength, pain, and Tegner score, as well as ultrasound image features and the ability to return to sports practice. Results: The average time of the first evaluation of the injury was 8.75 weeks. All patients presented muscle strength grade V after eight weeks. The pain score evolved from 5.75 to 0.5 points of the visual analogue scale (VAS), at the end of the treatment. The Tegner score after treatment was six points on average. Patients returned to sports practice after 8.14 weeks. Conclusion: ESWT associated with physical therapy proved to be effective to treat long-term muscle injury, with good performance and the ability to return to sport practice for all patients. Level of Evidence IV, Case Series, Prospective Study.

Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors.

Depending on the inflammatory milieu, injury can result either in a tissue's complete regeneration or in its degeneration and fibrosis, the latter of which could potentially lead to permanent organ failure. Yet how inflammatory cells regulate matrix-producing cells involved in the reparative process is unknown. Here we show that in acutely damaged skeletal muscle, sequential interactions between multipotent mesenchymal progenitors and infiltrating inflammatory cells determine the outcome of the reparative process. We found that infiltrating inflammatory macrophages, through their expression of tumor necrosis factor (TNF), directly induce apoptosis of fibro/adipogenic progenitors (FAPs). In states of chronic damage, however, such as those in mdx mice, macrophages express high levels of transforming growth factor β1 (TGF-β1), which prevents the apoptosis of FAPs and induces their differentiation into matrix-producing cells. Treatment with nilotinib, a kinase inhibitor with proposed anti-fibrotic activity, can block the effect of TGF-β1 and reduce muscle fibrosis in mdx mice. Our findings reveal an unexpected anti-fibrotic role of TNF and suggest that disruption of the precisely timed progression from a TNF-rich to a TGF-β-rich environment favors fibrotic degeneration of the muscle during chronic injury.

Outcome of transfer of the sternal head of the pectoralis major with its bone insertion to the scapula to manage scapular winging

The purpose of this study was to evaluate the outcome of transfer of the sternal head of the pectoralis major with its bone insertion to the inferior pole of the scapula for symptomatic winging. Our study included 51 patients with serratus anterior dysfunction secondary to chronic muscle or long thoracic nerve injury. Indications included pain, scapular winging, and limited active motion after failed conservative management. All patients underwent transfer of the sternal head of the pectoralis major with its bone insertion to the scapular inferior pole. Computed tomography scan was performed at 3 months postoperatively to evaluate bone healing. At an average follow-up of 29 months (range, 12-46 months), 45 patients had complete and 6 patients had partial resolution of the scapular winging. Patients had significant improvements in their shoulder abduction, forward flexion, and pain levels (P < .01). The mean shoulder Constant score improved from 49 preoperatively to 82 postoperatively; the shoulder subjective value improved from 60% to 84%; and the Disabilities of the Arm, Shoulder, and Hand score improved from 58 to 14 (P < .01). Computed tomography scans at an average of 3 months postoperatively demonstrated full healing in 41 patients and partial healing in 10. Pectoralis major transfer of the sternal head with its bone insertion to the inferior pole of the scapula is a reliable transfer to stabilize and to restore the function of the scapula in patients with symptomatic winging. This technique allows the ability to directly transfer the tendon to the scapula with bone-to-bone healing, leading to faster healing and a quicker return to unrestricted activities.

Simvastatin reduces myosteatosis after skeletal muscle injury (1163.19)

Chronic skeletal muscle injuries or tears can lead to the induction of myosteatosis, which is muscle atrophy combined with an accumulation of lipid plaques. Simvastatin is a drug that has demonstrated the ability to prevent lipid accumulation in other injured tissues. We hypothesized that administering simvastatin would reduce myosteatosis following muscle injuries. As the rotator cuff muscle group is especially prone to the development of myosteatosis, to test our hypothesis we performed a full‐thickness supraspinatus tenectomy and administered vehicle or simvastatin for 4 weeks. Compared to controls, simvastatin treatment increased muscle fiber specific force by 19% and decreased visible fat around fibers. Expression of several genes associated with fat accumulation, inflammation, macrophage accumulation, and extracellular matrix fibrosis was significantly decreased. Simvastatin also reduced the percent of pathological type IIB muscle fibers by 39%. These results suggest that simvastatin can protect muscles from the development of myosteatosis, and be useful in the clinical treatment of chronic muscle injuries and tears.

Antagonizing PPARγ improves muscle fiber force production and reduces lipid infiltration following chronic muscle injury (1163.20)

Following chronic tears, certain muscle groups develop an accumulation of ectopic fat within muscle fibers, as well as in plaques within the extracellular matrix. Muscle atrophy, fibrosis and inflammation often accompany this fat infiltration, and these changes are commonly referred to as “fatty degeneration.” As PPARγ is a potent inducer of adipogenesis, we tested the hypothesis that antagonizing PPARγ signaling would reduce fatty degeneration and increase muscle fiber specific force production in a rat full‐thickness severe rotator cuff tear model. Rats were subjected to a full thickness tenectomy of the supraspinatus and infraspinatus tendons and received either standard chow or chow infused with the PPARγ antagonist GW9662. Thirty days after tear, muscles were harvested and prepared for muscle fiber contractility, histology, and RNA isolation. Compared with control rats, torn muscles from PPARγ antagonist rats exhibited a 15% increase in specific force production. Additionally, antagonizing PPARγ reduced the amount of lipid plaques, along with a downregulation of several mRNA transcripts involved in canonical muscle lipid metabolism, macrophage accumulation, atrophy, autophagy and fibrosis. While further studies are necessary, the results from the current work support PPARγ as a potential therapeutic target for the treatment of fatty degeneration in chronic muscle tears.