scholarly journals Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans

2013 ◽  
Vol 115 (6) ◽  
pp. 937-948 ◽  
Author(s):  
Edward K. Merritt ◽  
Michael J. Stec ◽  
Anna Thalacker-Mercer ◽  
Samuel T. Windham ◽  
James M. Cross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cell Signaling ◽  
Vastus Lateralis ◽  
Receptor Expression ◽  
Vastus Lateralis Muscle ◽  
Regenerative Capacity ◽  
Muscle Inflammation ◽  
Tnf Α

The regenerative response of skeletal muscle to mechanically induced damage is impaired with age. Previous work in our laboratory suggests this may result from higher proinflammatory signaling in aging muscle at rest and/or a greater inflammatory response to damage. We, therefore, assessed skeletal muscle proinflammatory signaling at rest and 24 h after unaccustomed, loaded knee extension contractions that induced modest muscle damage (72% increase in serum creatine kinase) in a cohort of 87 adults across three age groups (AGE40, AGE61, and AGE76). Vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways were determined by quantitative PCR and immunoblot analysis. For in vitro studies, cell signaling and fusion capacities were compared among primary myoblasts from young (AGE28) and old (AGE64) donors treated with TNF-α. Muscle expression was higher (1.5- to 2.1-fold) in AGE76 and AGE61 relative to AGE40 for several genes involved in IL-6, TNF-α, and TNF-like weak inducer of apoptosis signaling. Indexes of activation for the proinflammatory transcription factors signal transducer and activator of transcription-3 and NF-κB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, muscle RING finger 1, and atrogin-1, and increased TNF-like weak inducer of apoptosis receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media and greater NF-κB activation in response to TNF-α treatment (compared with AGE28). We show for the first time that human aging is associated with muscle inflammation susceptibility (i.e., higher basal state of proinflammatory signaling) that is present in both tissue and isolated myogenic cells and likely contributes to the impaired regenerative capacity of skeletal muscle in the older population.

Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run

2003 ◽  
Vol 94 (5) ◽  
pp. 1917-1925 ◽  
Author(s):  
D. C. Nieman ◽  
J. M. Davis ◽  
D. A. Henson ◽  
J. Walberg-Rankin ◽  
M. Shute ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Vastus Lateralis ◽  
Maximal Oxygen Consumption ◽  
Vastus Lateralis Muscle ◽  
Cytokine Mrna ◽  
Carbohydrate Ingestion ◽  
Muscle Glycogen Content ◽  
Tnf Α

Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% maximal oxygen consumption (V˙o 2 max) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla ( P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-α, IL-8, IL-1β, IL-12p35, IL-6, and IFN-γ. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1β, IL-6, and IL-8 (large increases), and IL-10 and TNF-α (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 ( P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70%V˙o 2 max despite no differences in muscle glycogen content.

Effects of eccentric treadmill exercise on inflammatory gene expression in human skeletal muscle

2009 ◽  
Vol 34 (4) ◽  
pp. 745-753 ◽  
Author(s):  
Thomas W. Buford ◽  
Matthew B. Cooke ◽  
Brian D. Shelmadine ◽  
Geoffrey M. Hudson ◽  
Liz Redd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Soreness ◽  
Vastus Lateralis ◽  
Maximal Oxygen Consumption ◽  
Housekeeping Gene ◽  
Necrosis Factor Alpha ◽  
Muscle Gene Expression ◽  
Tnf Α

The present study examined the skeletal muscle expression of several genes related to the inflammatory process before and after a bout of downhill running. Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill (–17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods samples and muscle biopsy samples from the vastus lateralis were donated prior to and at 3-h and 24-h postexercise, along with ratings of perceived muscle soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha (TNF-α), IL-1β, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB) (p105/p50). Gene expression was analyzed using RT-PCR and compared with a standard housekeeping gene (β-actin). Data were analyzed for statistical differences using multivariate analysis of variance with univariate follow-up. In addition, Pearson correlations were conducted to determine if any significant relationship exists between any of these transcripts and both CK and muscle soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA expression were observed compared with baseline, whereas no significant changes for IL-12, IL-1β, TNF-α, or NFkB were noted. Significant increases in IL-6 mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h postexercise. In addition, muscle soreness was significantly correlated with IL-8 at 24 h (r = –0.370; p = 0.048), whereas CK was significantly related to NFkB at baseline (r = –0.460; p = 0.012). These data indicate that increases in the mRNA expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of damaging eccentric exercise in young, recreationally trained males. Further, it appears that IL-8 transcription may play some role in inhibiting postexercise muscle soreness, possibly through regulation of angiogenesis.

scholarly journals Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons

2008 ◽  
Vol 105 (2) ◽  
pp. 473-478 ◽  
Author(s):  
Charles P. Lambert ◽  
Nicole R. Wright ◽  
Brian N. Finck ◽  
Dennis T. Villareal
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Vastus Lateralis ◽  
Exercise Group ◽  
Fat Free Mass ◽  
Vastus Lateralis Muscle ◽  
Elderly Persons ◽  
Chronic Inflammatory Response ◽  
Tnf Α ◽  
Weight Loss Group

Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (∼7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-α, and IL-6 in 16 obese (body mass index 38 ± 2 kg/m2) older (69 ± 1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time RT-PCR. Body composition was assessed by dual-energy x-ray absorptiometry. Body weight decreased (−7.5 ± 1.2 kg, P = 0.001) in the weight loss group but not in the exercise group (−0.3 ± 0.8 kg, P = 0.74). Fat-free mass (FFM) decreased (−2.9 ± 0.6 kg, P = 0.010) in the weight loss group and increased (1.6 ± 0.6 kg, P = 0.03) in the exercise group. Exercise resulted in a 37% decrease in TLR-4 mRNA ( P < 0.05) while weight loss had no significant effect. Additionally, exercise led to a significant (50%) decrease in IL-6 and TNF-α mRNA ( P < 0.05) while weight loss had no effect. Exercise increased MGF mRNA (∼2 fold, P < 0.05), but weight loss had no effect. In conclusion, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals.

scholarly journals Exercise training improves neurovascular control and calcium cycling gene expression in patients with heart failure with cardiac resynchronization therapy

2016 ◽  
Vol 311 (5) ◽  
pp. H1180-H1188 ◽  
Author(s):  
Thais S. Nobre ◽  
Ligia M. Antunes-Correa ◽  
Raphaela V. Groehs ◽  
Maria Janieire N. N. Alves ◽  
Adriana O. Sarmento ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Cardiac Resynchronization Therapy ◽  
Exercise Capacity ◽  
Receptor Expression ◽  
Cardiac Resynchronization ◽  
Vastus Lateralis Muscle ◽  
Resynchronization Therapy

Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca2+-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o2 peak, MSNA (microneurography), forearm blood flow, and Ca2+-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o2 peak were significantly increased in the ET group ( P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET ( P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET ( P = 0.0004), but not in the NoET, group. The expression of the Na+/Ca2+ exchanger ( P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca2+-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.

Influence of carbohydrate ingestion on immune changes after 2 h of intensive resistance training

2004 ◽  
Vol 96 (4) ◽  
pp. 1292-1298 ◽  
Author(s):  
D. C. Nieman ◽  
J. M. Davis ◽  
V. A. Brown ◽  
D. A. Henson ◽  
C. L. Dumke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glycogen Content ◽  
Weight Training ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Carbohydrate Ingestion ◽  
Trained Subjects ◽  
Muscle Gene Expression ◽  
Cell Counts ◽  
Tnf Α

Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo (Pla) groups and lifted weights for 2 h (10 exercises, 4 sets each, 10 repetitions, with 2- to 3-min rest intervals). Subjects received 10 ml·kg-1·h-1 CHO (6%) or Pla beverages during the weight training bout. Blood, saliva, and vastus lateralis muscle biopsy samples were collected before and after exercise. Blood cell counts were determined, and plasma was analyzed for IL-6, IL-10, IL-1 receptor antagonist (IL-1ra), IL-8, and cortisol. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-γ, TNF-α) by use of real-time quantitative RT-PCR. Significant but modest increases were measured for plasma IL-6, IL-10, IL-1ra, and IL-8, but the pattern of increase did not differ between CHO and Pla groups. The rate of decrease in muscle glycogen content did not differ between CHO and Pla ( P = 0.463). Muscle cytokine mRNA was detected preexercise for IL-1β, IL-6, IL-15, IL-8, and TNF-α, and of these, IL-1β, IL-6, IL-8, and TNF-α were significantly increased after the 2-h weight training bout. The increase in mRNA (fold difference from preexercise) did not differ between CHO and Pla groups. In summary, CHO vs. Pla ingestion did not alter modest increases measured for plasma IL-6, IL-10, IL-1ra, and IL-8, and muscle gene expression for IL-1β, IL-6, IL-8, and TNF-α in strength-trained subjects lifting weights intensively for 2 h.

Endurance training alters antioxidant enzyme gene expression in rat skeletal muscle

1998 ◽  
Vol 76 (12) ◽  
pp. 1139-1145 ◽  
Author(s):  
M Gore ◽  
R Fiebig ◽  
J Hollander ◽  
C Leeuwenburgh ◽  
H Ohno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Protein Content ◽  
Endurance Training ◽  
Vastus Lateralis ◽  
Mrna Abundance ◽  
Vastus Lateralis Muscle ◽  
Sod Activity

The effects of endurance training on gene expression of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were investigated in type 2a and 2b skeletal muscles, as well as heart and liver, in the rat. Female Sprague-Dawley rats (4 months old, 300-320 g) were randomly divided into a trained (T, n = 11) and a control (C, n = 10) group and were pair fed a diet consisting of 66% cornstarch and 34% basal diet that contained all essential nutrients. Training was conducted on a treadmill at 25 m·min-1, 10% grade for 2 h per day, 5 days per week for 10 weeks, resulting in a 79% (p < 0.01) increase in citrate synthase activity in the deep portion of vastus lateralis muscle (DVL, type 2a). Cu-Zn SOD activity was 35% higher (p < 0.01) in DVL of T versus C rats, and Cu-Zn SOD mRNA abundance showed a 125% increase with training (p < 0.05). Cu-Zn SOD protein content was not altered in DVL, but increased significantly (p < 0.05) in the superficial portion of vastus lateralis (type 2b) with training. Trained rats showed a 66% higher (p < 0.05) Mn SOD protein content in DVL, but Mn SOD activity and mRNA abundance were not affected. Training also significantly increased GPX activity by 62% (p < 0.05), without changing its mRNA abundance, in the DVL. Heart and liver showed a 112 and 58% increase (p < 0.01) in Cu-Zn SOD mRNA abundance with training, respectively, but no other training adaptation was detected. These data indicate that endurance training can promote gene expression of muscle antioxidant enzymes in a fiber-specific manner. Training appears to upregulate Cu-Zn SOD mRNA abundance in a number of aerobic tissues, whereas Mn SOD and GPX induction observed in DVL may occur at the post-transcriptional levels.Key words: glutathione peroxidase, mRNA, skeletal muscle superoxide dismutase, training.

Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women

2005 ◽  
Vol 99 (5) ◽  
pp. 1872-1879 ◽  
Author(s):  
Andrea N. Croley ◽  
Kevin A. Zwetsloot ◽  
Lenna M. Westerkamp ◽  
Nicholas A. Ryan ◽  
Angela M. Pendergast ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Muscle Fibers ◽  
Receptor Expression ◽  
Vastus Lateralis Muscle ◽  
Vegf Receptor ◽  
Type I ◽  
Type Ii ◽  
Vegf Mrna ◽  
Vegf Protein

In humans, the majority of studies demonstrate an age-associated reduction in the number of capillaries surrounding skeletal muscle fibers; however, recent reports in rats suggest that muscle capillarization is well maintained with advanced age. In sedentary and trained men, aging lowers the number of capillaries surrounding type II, but not type I, skeletal muscle fibers. The fiber type-specific effect of aging on muscle capillarization is unknown in women. Vascular endothelial growth factor (VEGF) is important in the basal maintenance of skeletal muscle capillarization, and lower VEGF expression is associated with increased age in nonskeletal muscle tissue of women. Compared with young women (YW), we hypothesized that aged women (AW) would demonstrate 1) lower muscle capillarization in a fiber type-specific manner and 2) lower VEGF and VEGF receptor expression at rest and in response to acute exercise. Nine sedentary AW (70 + 8 yr) and 11 YW (22 + 3 yr) had vastus lateralis muscle biopsies obtained before and at 4 h after a submaximal exercise bout for the measurement of morphometry and VEGF and VEGF receptor expression. In AW compared with YW, muscle capillary contacts were lower overall (YW: 2.36 + 0.32 capillaries; AW: 2.08 + 0.17 capillaries), specifically in type II (YW: 2.37 + 0.39 capillaries; AW: 1.91 + 0.36 capillaries) but not type I fibers (YW: 2.36 + 0.34 capillaries; AW: 2.26 + 0.24 capillaries). Muscle VEGF protein was 35% lower at rest, and the exercise-induced increase in VEGF mRNA was 50% lower in AW compared with YW. There was no effect of age on VEGF receptor expression. These results provide evidence that, in the vastus lateralis of women, 1) capillarization surrounding type II muscle fibers is lower in AW compared with YW and 2) resting VEGF protein and the VEGF mRNA response to exercise are lower in AW compared with YW.

scholarly journals Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques

2014 ◽  
Vol 306 (11) ◽  
pp. R837-R844 ◽  
Author(s):  
Liz Simon ◽  
Nicole LeCapitaine ◽  
Paul Berner ◽  
Curtis Vande Stouwe ◽  
Jason C. Mussell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myogenic Differentiation ◽  
Rhesus Macaques ◽  
In Vitro Assays ◽  
Regenerative Capacity ◽  
Differentiation Potential ◽  
Myotube Formation ◽  
Significant Difference

Chronic alcohol abuse is associated with skeletal muscle myopathy. Previously, we demonstrated that chronic binge alcohol (CBA) consumption by rhesus macaques accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus (SIV) infection. A proinflammatory, prooxidative milieu and enhanced ubiquitin proteasome activity were identified as possible mechanisms leading to loss of skeletal muscle. The possibility that impaired regenerative capacity, as reflected by the ability of myoblasts derived from satellite cell (SCs) to differentiate into myotubes has not been examined. We hypothesized that the inflammation and oxidative stress in skeletal muscle from CBA animals impair the differentiation capacity of myoblasts to form new myofibers in in vitro assays. We isolated primary myoblasts from the quadriceps femoris of rhesus macaques that were administered CBA or isocaloric sucrose (SUC) for 19 mo. Proliferation and differentiation potential of cultured myoblasts were examined in vitro. Myoblasts from the CBA group had significantly reduced PAX7, MYOD1, MYOG, MYF5, and MEF2C expression. This was associated with decreased myotube formation as evidenced by Jenner-Giemsa staining and myonuclei fusion index. No significant difference in the proliferative ability, cell cycle distribution, or autophagy was detected between myoblasts isolated from CBA and SUC groups. Together, these results reflect marked dysregulation of myoblast myogenic gene expression and myotube formation, which we interpret as evidence of impaired skeletal muscle regenerative capacity in CBA-administered macaques. The contribution of this mechanism to alcoholic myopathy warrants further investigation.

A microcalorimetric study of heat production in resting skeletal muscle from human subjects

1986 ◽  
Vol 70 (1) ◽  
pp. 63-72 ◽  
Author(s):  
B. Fagher ◽  
M. Monti ◽  
I. Wadsö
Keyword(s):  
Skeletal Muscle ◽  
Heat Production ◽  
Human Subjects ◽  
Vastus Lateralis ◽  
Surrounding Medium ◽  
Muscle Metabolism ◽  
Heat Evolution ◽  
Vastus Lateralis Muscle ◽  
Fibre Bundles

1. Different microcalorimetric techniques have been compared for the assessment in vitro of the total metabolic activity of resting skeletal muscle. Human fibre bundles were suspended in Krebs-Ringer-phosphate buffer containing glucose and insulin and the heat evolution was continuously monitored for 2–6 h. Palmitate as substrate was also tested. 2. The power signals declined rapidly when a static calorimetric method (A) was used. Two different perfusion methods (B, C) gave higher power values. Long-lasting steady states were observed with method C, where the sample was contained in a cage acting as a stirrer. 3. Significant differences were found for fibre bundles from different human muscles as well as age- and sex-related differences. The heat production in samples from the rectus abdominis muscle (method B), 0.73 mW/g muscle wet wt., was significantly higher than for the obliquus internus muscle, 0.44 mW/g, and the vastus lateralis muscle, 0.55 mW/g, but not different from the heat production value of vastus medialis, 0.66 mW/g. 4. In method C particularly, the fibre bundles are believed to be in adequate contact with the surrounding medium. With the use of a multichannel calorimeter it is possible to perform up to four experiments simultaneously, e.g. involving the calorigenic effects of pharmacological substances. The technique provides a new approach for detailed studies of muscle metabolism in physiological and pathological conditions.

Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice

2021 ◽  
Vol 49 (2) ◽  
pp. 332-339
Author(s):  
Hideyuki Shirasawa ◽  
Noboru Matsumura ◽  
Masaki Yoda ◽  
Kazumasa Okubo ◽  
Masayuki Shimoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Gene Expression Analysis ◽  
Retinoic Acid Receptor ◽  
Adipogenic Differentiation ◽  
Fatty Infiltration ◽  
Cuff Tear

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.

Sign in / Sign up

Export Citation Format

Share Document