Acute Muscle Injury Research Articles

Cross-cultural adaptation, reliability and validity of the persian version of the functional assessment scale for acute hamstring injuries

BackgroundThe Functional Assessment Scale for Acute Hamstring Injuries (FASH) which measure symptom’s severity and impact on physical activity and sports ability in individuals with acute hamstring muscle injury, is not available in Persian. The aim of this study was to translate and cross-culturally adapt the FASH questionnaire to Persian and to assess the psychometric properties of the translated version.MethodsThe Persian-translation and cross-cultural adaptation processes were based on World Health Organization method. A total of 160 participants compromising of four groups: (1) acute hamstring injury (N = 40), (2) other lower extremity injury (N = 40), (3) risk of acute injury (N = 40), and (4) healthy control (N = 40) were recruited to complete the Persian version of FASH (FASH-P) questionnaire twice with an interval of 48–60 h. The Short Form Health Survey (SF-36) and Lower Extremity Functional Scale (LEFS) were used to assess the criterion validity. Test-retest reliability, internal consistency, criterion validity, Dimensionality and floor/ceiling effects were evaluated to assess the FASH-P psychometric properties.ResultsThe FASH questionnaire were translated to Persian without any major problems. The FASH-P showed excellent power of differentiation because the scores were significantly different among the four groups. Regarding psychometric performances, excellent test–retest reliability (Intraclass correlation coefficient of 0.997) and a high level of internal consistency (Cronbach’s alpha of 0.966) were observed. The FASH-P total score was significantly correlated with SF-36 and LEFS questionnaires representing an excellent criterion validity. No floor or ceiling effect were found for total score in Hamstring muscle injury group.ConclusionsDue to the excellent psychometric performance, the FASH-P can be used as a reliable and valid tool for evaluating the severity of symptoms and sports ability in Persian-speaking patients with hamstring muscle injury.

Platelet-Poor Plasma for the Treatment of Acute Hamstring Muscle Injuries in Collegiate Football Athletes: A Cohort Study.

To evaluate the efficacy of platelet-poor plasma injections for the treatment of acute hamstring muscle strains. Cohort study. Outpatient Sports Medicine Clinic. Twenty consecutive patients with an acute hamstring muscle injury from 2021 to 2022 were included. Platelet-poor plasma injection into the hamstring muscle strain. Time (days) until return to full unrestricted participation in sport. All patients were male collegiate football athletes, with an average age of 20 (±1.6) years old. The most commonly injured muscle was the semitendinosus (65%). After treatment with platelet-poor plasma, patients on average returned to full, unrestricted participation in sport at 29.4 (±7.2) days postinjury, with a statistically significant improvement in pain as early as 2 weeks postinjection. No recurrent injuries to the affected hamstring muscles were seen within 12 months. PPP may be a safe and effective treatment for acute hamstring muscle strains and may potentially expedite time to return to play.

E2 signaling in myofibers promots macrophage efferocytosis in mouse skeletal muscles with cardiotoxin-induced acute injury

To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury. Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury, followed by intramuscular injection of β-estradiol (E2) or 4-hydroxytamoxifen (4-OHT). The changes in serum E2 of the mice were detected using ELISA, and the number, phenotypes, and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry. C2C12 cells were induced to differentiate into mature myotubes, which were treated with IFN- γ for 24 before treatment with β -Estradiol or 4-OHT. The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio, followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation, and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry. Compared with the control mice, the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates, with increased M1 cell percentage, reduced M2 cell percentage and macrophage efferocytosis in the injured muscle, and obviously delayed myofiber regeneration and repair. In the cell co-culture systems, treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis, while 4-OHT treatment resulted in the opposite changes. In injured mouse skeletal muscles, myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis, thereby relieving inflammation and promoting muscle regeneration and repair.

Role of High Frequency Ultrasound in Assessment of Acute and Chronic Muscle Injuries in Comparison to MRI

Abstract Background The most common mechanism of injury of muscles is related to muscle strain (indirect muscle injury), mainly in the lower limbs. Muscles are at risk for disruption during eccentric contraction, as the force of active contraction is added to the passive stretching force applied to the myotendinous junction (MTJ). Although clinical examinations remain very important, it has been shown that radiological findings can aid clinicians in the initial assessment. Objective To evaluate the accuracy and specificity of high frequency ultrasound in identification and characterization of acute and chronic muscle injuries in comparison with MRI. Methods This ultrasonography & cross sectional study was done in private radiological centers with a period of 24 months on a random sample of 30 patients. Our study included 30 patients complaining of traumatic acute and chronic muscle injuries, 26 males (86.7%) and 4 females (13.3%), ranging in age from 18 to 55 years with a mean age of 37.5 years. Results The accuracy, sensitivity & specificity of ultrasound in detecting all muscle injuries in comparison to MRI: 86.7%, 87.5% & 83.3% respectively. The accuracy, sensitivity & specificity of ultrasound in detecting acute muscle injuries in comparison to MRI: 66.7%, 66.7 % & 66.7% respectively. The accuracy, sensitivity & specificity of ultrasound in detecting chronic muscle injuries in comparison to MRI: 95.2%, 94.4% & 100% respectively. Conclusion Ultrasound is highly operator dependent, useful for diagnosis of chronic muscle injury in comparison to the MRI, yet with pitfalls in acute muscle injuries, yet the ultrasound classification criteria for muscle injury can be used to predict the severity of injury and guide decision on the type of treatment and MRI is still considered the main diagnostic tool for muscle injuries and classification.

Characterization of Age-Dependent Changes in Skeletal Muscle Repair and Regeneration Using a Mouse Model of Acute Muscle Injury.

Acute skeletal muscle injury initiates a process of necrosis, debris clearance, and ultimately tissue regeneration via myogenesis. While skeletal muscle stem cells (MuSCs) are responsible for populating the proliferative myogenic progenitor pool to fuel muscle repair, recruited and resident immune cells have a central role in the regulation of muscle regeneration via the execution of phagocytosis and release of soluble factors that act directly on MuSCs to regulate myogenic differentiation. Therefore, the timing of MuSC proliferation and differentiation is closely linked to the populations and behaviors of immune cells present within skeletal muscle. This has important implications for aging andmuscle repair, as systemic changes in immune system function contribute to a decline in muscle regenerative capacity. Here, we present adapted protocols for the isolation of mononuclear cells from skeletal muscles for the quantification of immune cell populations using flow cytometry. We also describe a cardiotoxin skeletal muscle injury protocol and detail the expected outcomes including immune cell infiltration to the injured sites and formation of new myocytes. As immune cell function is substantially influenced by aging, we extend these approaches and outcomes to aged mice.

Effects of radial extracorporeal shock wave with different frequencies on acute skeletal muscle injury in rabbits

To study the efficacy and possible mechanisms of radial extracorporeal shock wave (rESW) with different frequencies for the treatment of acute skeletal muscle injury in rabbits, 48 rabbits of acute injured biceps femoris were randomly divided into 4 groups. Except for the control group, the other groups were treated by rESW with 5 Hz, 10 Hz and 15 Hz, respectively. The injury symptom index scores (ISISs) in the rESW group were significantly lower than those in the control group, with the lowest in the 10 Hz rESW group. Histomorphological features demonstrated a decrease in mononuclear cells and an increase in new myocytes across all groups, with the rESW group showing the most significant changes. The concentrations of PGE2 and IL-1β were significantly lower in all rESW groups by ELISA compared to the control group. Additionally, the 10 Hz group had lower concentrations than the 5 Hz and 15 Hz group. Compared with the control group, MyoD of the rESW groups was significantly increased, and the expression level of the 10 Hz group was higher than that of the other groups. In conclusion, rESW with 5 Hz, 10 Hz and 15 Hz take certain curative effects on acute biceps femoris injury in rabbits, and the 10 Hz rESW takes advantage over 5 Hz and 15 Hz rESW.

Curcumin-activated Wnt5a pathway mediates Ca2+ channel opening to affect myoblast differentiation and skeletal muscle regeneration.

Skeletal muscle injury is one of the most common sports injuries; if not properly treated or not effective rehabilitation treatment after injury, it can be transformed into chronic cumulative injury. Curcumin, an herbal ingredient, has been found to promote skeletal muscle injury repair and regeneration. The Wnt5a pathway is related to the expression of myogenic regulatory factors, and Ca2+ promotes the differentiation and fusion process of myoblasts. This study explored the effect and mechanism of curcumin on myoblast differentiation during the repair and regeneration of injured skeletal muscle and its relationship with the Wnt5a pathway and Ca2+ channel. Myogenic differentiation of C2C12 cells was induced with 2% horse serum, and a mouse (male, 10weeks old) model of acute skeletal muscle injury was established using cardiotoxin (20μL). In addition, we constructed a Wnt5a knockdown C2C12 cell model and a Wnt5a knockout mouse model. Besides, curcumin was added to the cell culture solution (80mg/L) and fed to the mice (50mg/kg). Fluorescence microscopy was used to determine the concentration of Ca2+. Western blot and RT-qPCR were used to detect the protein and mRNA levels of Wnt5a, CaN, NFAT2, MyoD, Myf5, Pax7, and Myogenin. The expression levels of MyoD, Myf5, Myogenin, MHC, Desmin, and NFAT2 were detected using immunofluorescence techniques. In addition, MyoD expression was observed using immunohistochemistry, and morphological changes in mouse muscle tissue were observed using HE staining. During myoblast differentiation and muscle regeneration, Wnt5a expression was upregulated (P<0.001) and the Wnt5a signalling pathway was activated. Wnt5a overexpression promoted the expression of MyoD, Myf5, Myogenin, MHC, and Desmin (P<0.05), and conversely, knockdown of Wnt5a inhibited their expression (P<0.001). The Wnt5a pathway mediated the opening of Ca2+ channels, regulated the expression levels of CaN, NFAT2, MyoD, Myf5, Myogenin, MHC, and Desmin (P<0.01) and promoted the differentiation of C2C12 myoblasts and the repair and regeneration of injured skeletal muscle. The expression of Wnt5a, CaN, NFAT2, MyoD, Myogenin, Myf5, and MHC in C2C12 myoblast was significantly increased after curcumin intervention (P<0.05); however, their expression decreased significantly after knocking down Wnt5a on the basis of curcumin intervention (P<0.05). Similarly, in Wnt5a knockout mice, the promotion of muscle regeneration by curcumin was significantly attenuated. Curcumin can activate the Wnt5a signalling pathway and mediate the opening of Ca2+ channels to accelerate the myogenic differentiation of C2C12 cells and the repair and regeneration of injured skeletal muscle.

Platelet-Poor vs Platelet-Rich Plasma For The Treatment Of Acute Thigh Muscle Injuries.

The aim of this study was to determine whether patients treated with platelet-poor plasma (PPP) after an acute thigh muscle injury would have a faster return to activity compared to patients treated with platelet-rich plasma (PRP). This quasi-experimental study included 100 patients (ages 16-45) with an acute thigh muscle injury diagnosed by sports ultrasound and treated with either PRP or PPP followed by a course of structured rehabilitation. The primary outcome was the number of days until unrestricted participation in sport, while the secondary outcome was the rate of recurrent injury within 12 months. The time until full, unrestricted participation in sport was significantly lower in the PPP group compared to the PRP group for all injury grades, with patients in the PPP group on average returning to unrestricted participation in sport 22.89 days more quickly than the PRP group (p < 0.001). Additionally, no significant difference in recurrent injury up to 12 months post-procedure was seen between groups (p = 0.967). PPP resulted in faster return to sport than PRP for acute thigh muscle injuries with a non-inferior injury recurrence rate. These findings suggest that future high level studies comparing PPP and PRP for the treatment of thigh muscle injuries should be considered.

P-787 Gestational diabetes in mice induces embryonic fibro-adipogenic progenitors memory that impedes the recovery of injured skeletal muscle in adult offspring

Abstract Study question Whether and how intrauterine hyperglycemia induced by Gestational diabetes steadily influences the function and fate of mesenchymal stem cells, specifically fibro-adipogenic progenitors. Summary answer Gestational diabetes in mice caused declines in self-renewal and paracrine in fibro-adipogenic progenitors, prompted adipogenesis and fibrosis, destroyed recovery after muscular injury in adult offspring. What is known already Gestational diabetes contributed to the increased susceptibility to metabolic disorders, cardiovascular diseases and atherosclerosis. Intrauterine hyperglycemia promoted placental inflammation and endowed the hematopoietic stem and progenitor cells. As an important mesenchymal stem cell, fibro-adipogenic progenitors (FAPs) play a key role in the process of “replace, repair, regeneration, restore and regress”. When acute injury happens to skeletal muscle, the fibro-adipogenic progenitors cluster start to renew itself and differentiate into functional cells like fibroblasts or adipocytes, secrete cytokines to nearby myoblasts, inducing myotube formation and muscle regeneration by cell-cell communication. Study design, size, duration Pregnant mice were randomly divided into control (CTR) and gestational diabetes (GDM) groups, GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while CTR group was treated with vehicle buffer. Only when random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. At 8 weeks of offspring, we intramuscular injected cardiotoxin (CTX) to induce acute tibialis anterior muscle injury. Participants/materials, setting, methods 7 days after CTX intramuscular injection (CTX-D7) in offspring, mice were sacrificed and tiabialis anterior muscle was selected. Perilipin immunochemical and immunofluorescent staining, MASSON and Sirius Red staining were used to evaluate the recovery extent between CTR and GDM groups. Then we used fluorescence-activated cell sorting to evaluate the self proliferation of fibro-adipogenic cells at CTX-D3. We also collected FAPs to perform induced differentiation in vitro, co-culture with myoblast and SMART-sequence to explore underlying mechanism. Main results and the role of chance 7 days after cardiotoxin injection (CTX-D7), we used WGA to mark injured myofibers, eMHC to mark regenerated myofibers. Immunofluorescence and hematoxylin-eosin staining showed the muscle fibers in GDM male were still severe damaged and inadequate recovered when compared to CTR group. Perilipin immunochemical staining demonstrated more lipids deposition in GDM male muscle. MASSON and Sirius Red staining also revealed increased accumulation of collagen fibers in GDM group. Fluorescence-activated cell sorting firstly displayed depletion in numbers of Lineage-VCAM-Sca-1+ fibro-adipogeneic progenitors (FAPs) compartment in GDM group at CTX-D3 compared to CTR group. Using α-SMA to mark collagen fibers, perilipin to mark adiposity cells, we also observed activation of the FAPs into fibrosis or adipogenesis by in vitro induced differentiation. Myotubes formation experiment showed that myotubes were thinner and fusion extent was worse in myoblasts co-cultured with GDM FAPs rather than CTR FAPs. Finally, we performed SMART-sequence of FAPs between groups. Regarding p &amp;lt; 0.05 and the absolute of log2 foldchange &amp;gt;1 as significance, we totally found 1572 down-regulated genes, 1527 up-regulated genes in GDM FAPs. And the GO term analysis showed us that WNT signaling pathway, cell surface receptor signaling pathway were most highly affected. Limitations, reasons for caution We haven’t found out the key molecule in WNT signaling pathway, and how intrauterine hyperglycemia steadily affected FAP’s function remains to be explored. Also, whether other mesenchymal stem cells are influenced by short-term intrauterine hyperglycemia needs to be clarified. Wider implications of the findings Fibro-adipogenic progenitors is an important part of mesenchymal stem cells. These results demonstrated GDM in mice might induce mesenchymal memory that affects the long-term health of the offspring, which reminds us the stemness of GDM progenitors or stem cells might be destroyed and its cell-cell function may be also damaged. Trial registration number ZJU20210047

P7C3 ameliorates barium chloride-induced skeletal muscle injury activating transcriptomic and epigenetic modulation of myogenic regulatory factors.

Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the nicotinamide phosphoribosyltransferase (Nampt) activator P7C3 improves muscle repair following injury. In the present study, we tested the effect of P7C3 (1-anilino-3-(3,6-dibromocarbazol-9-yl) propan-2-ol) on chemically induced muscle injury. Muscle injury was induced by injecting 50 µL 1.2% barium chloride (BaCl2) into the tibialis anterior (TA) muscle in C57Bl/6J wild-type male mice. Mice were then treated with either 10 mg/kg body weight of P7C3 or Vehicle intraperitoneally for 7 days and assessed for histological, biochemical, and molecular changes. In the present study, we show that the acute BaCl2-induced TA muscle injury was robust and the P7C3-treated mice displayed a significant increase in the total number of myonuclei and blood vessels, and decreased serum CK activity compared with vehicle-treated mice. The specificity of P7C3 was evaluated using Nampt+/- mice, which did not display any significant difference in muscle repair capacity among treated groups. RNA-sequencing analysis of the injured TA muscles displayed 368 and 212 genes to be exclusively expressed in P7C3 and Veh-treated mice, respectively. There was an increase in the expression of genes involved in cellular processes, inflammatory response, angiogenesis, and muscle development in P7C3 versus Veh-treated mice. Conversely, there is a decrease in muscle structure and function, myeloid cell differentiation, glutathione, and oxidation-reduction, drug metabolism, and circadian rhythm signaling pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) and reverse transcription-qPCR analyses identified increased Pax7, Myf5, MyoD, and Myogenin expression in P7C3-treated mice. Increased histone lysine (H3K) methylation and acetylation were observed in P7C3-treated mice, with significant upregulation in inflammatory markers. Moreover, P7C3 treatment significantly increased the myotube fusion index in the BaCl2-injured human skeletal muscle in vitro. P7C3 also inhibited the lipopolysaccharide-induced inflammatory response and mitochondrial membrane potential of RAW 264.7 macrophage cells. Overall, we demonstrate that P7C3 activates muscle stem cells and enhances muscle injury repair with increased angiogenesis.

Ultrasound in sports traumatology

Ultrasound (US) has numerous applications in sports traumatology. The technical progress of mobile US devices has led to increasing use of ultrasound as a primary diagnostic tool. New applications such as elastography and 3 D vascularization are used for special indications.The purpose of this review is to present the current status of ultrasound in the diagnosis of sports injuries and sport traumatology including established applications and new technical advances. US is presented both in its comparison to other imaging modalities and as a sole diagnostic tool.US can be used for initial diagnosis to improve the clinical examination and for intensive shortterm follow-up imaging. The main areas of application are currently the diagnosis of acute muscle and tendon injuries as well as overuse injuries. In particular, the exclusion of structural muscle injuries can be adequately ensured with US in the majority of anatomical regions. The recently published guideline on fracture ultrasound has strengthened the clinical evidence in this area, especially in comparison to conventional radiography and in the development of algorithms and standards. The increasing use of mobile ultrasound equipment with adequate image quality makes US a location-independent modality that can also be used at training sites or during road games.

Lineage tracing reveals a novel PDGFRβ+ satellite cell subset that contributes to myo-regeneration of chronically injured rotator cuff muscle

Massive rotator cuff (RC) tendon tears are associated with progressive fibro-adipogenesis and muscle atrophy that altogether cause shoulder muscle wasting. Platelet derived growth factor β (PDGFRβ) lineage cells, that co-express PDGFRα have previously been shown to directly contribute to scar formation and fat accumulation in a mouse model of irreversible tendon and nerve transection (TTDN). Conversely, PDGFRβ+ lineage cells have also been shown to be myogenic in cultures and in other models of skeletal muscle injury. We therefore hypothesized that PDGFRβ demarcates two distinct RC residing subpopulations, fibro-adipogenic and myogenic, and aimed to elucidate the identity of the PDGFRβ myogenic precursors and evaluate their contribution, if any, to RC myo-regeneration. Lineage tracing revealed increasing contribution of PDGFRβ+ myo-progenitors to the formation of GFP+ myofibers, which were the most abundant myofiber type in regenerated muscle at 2 weeks post-TTDN. Muscle regeneration preceded muscle atrophy and both advanced from the lateral site of tendon transection to the farthest medial region. GFP+/PDGFRβ+Sca-1−lin−CXCR4+Integrin-β1+ marked a novel subset of satellite cells with confirmed myogenic properties. Further studies are warranted to identify the existence of PDGFRβ+ satellite cells in human and other mouse muscles and to define their myo-regenerative potential following acute and chronic muscle injury.

Islr regulates satellite cells asymmetric division through the SPARC/p-ERK1/2 signaling pathway.

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.

Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice

BackgroundFree labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury, supporting platelet activation and thrombosis. ObjectivesTo investigate the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced platelet activation and arterial thrombosis. MethodsThe effect of hydroxychloroquine on hemin-induced platelet activation and hemolysis-induced platelet recruitment and aggregation was measured in washed platelets and hemolyzed blood, respectively. Its effect on ferric-chloride (FeCl3)-induced arterial thrombosis and lung perfusion following hemin injection was assessed in wild-type mice. ResultsErythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress. This thrombotic effect was reversed by hydroxychloroquine. In a purified system, hydroxychloroquine inhibited platelet build-up on immobilized von Willebrand factor in hemolyzed blood without altering initial platelet recruitment. Hydroxychloroquine inhibited hemin-induced platelet activation and phosphatidylserine exposure independently of reactive oxygen species generation. In the presence of hemin, hydroxychloroquine did not alter glycoprotein VI shedding but reduced C-type-lectin-like-2 expression on platelets. In vivo, hydroxychloroquine reversed pulmonary perfusion decline induced by exogenous administration of hemin. In arterial thrombosis models, hydroxychloroquine inhibited ferric-chloride–induced thrombosis in the carotid artery and reduced von Willebrand factor accumulation in the thrombi. ConclusionHydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thrombosis and to improve organ perfusion.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

ACETYL-COA PRODUCTION BY OCTANOIC ACID ALLEVIATES ACUTE COMPARTMENT SYNDROME-INDUCED SKELETAL MUSCLE INJURY THROUGH REGULATING MITOPHAGY.

Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a promising treatment for ACS owing to its potential ability to regulate metabolic/epigenetic pathways in ischemic injury. The present study was designed to investigate the efficacy and underlying mechanism of octanoic acid in ACS-induced skeletal muscle injury. Methods: In this study, we established a saline infusion ACS rat model. Subsequently, we assessed the protective effects of sodium octanoate (NaO, sodium salt of octanoic acid) on ACS-induced skeletal muscle injury. Afterward, the level of acetyl-coenzyme A and histone acetylation in the skeletal muscle tissue were quantified. Moreover, we investigated the activation of the AMP-activated protein kinas pathway and the occurrence of mitophagy in the skeletal muscle tissue. Lastly, we scrutinized the expression of proteins associated with mitochondrial dynamics in the skeletal muscle tissue. Results: The administration of NaO attenuated muscle inflammation, alleviating oxidative stress and muscle edema. Moreover, NaO treatment enhanced muscle blood perfusion, leading to the inhibition of apoptosis-related skeletal muscle cell death after ACS. In addition, NaO demonstrated the ability to halt skeletal muscle fibrosis and enhance the functional recovery of muscle post-ACS. Further analysis indicates that NaO treatment increases the acetyl-CoA level in muscle and the process of histone acetylation by acetyl-CoA. Lastly, we found NaO treatment exerts a stimulatory impact on the activation of the AMPK pathway, thus promoting mitophagy and improving mitochondrial dynamics. Conclusion: Our findings indicate that octanoic acid may ameliorate skeletal muscle injury induced by ACS. Its protective effects may be attributed to the promotion of acetyl-CoA synthesis and histone acetylation within the muscular tissue, as well as its activation of the AMPK-related mitophagy pathway.

Selection of aptamer for creatine Kinase-MM as a marker for muscular dystrophy and myocardial infarction

Creatine kinase-MM (CK-MM) is a relatively muscle-specific enzyme with a plasma half-life of approximately 2 h. Total creatine kinase elevation is evident in several conditions associated with acute muscle injury, severe muscular exertion, and myocardial infarction. The presence of a large amount of the CK-MM enzyme in blood serum is a biomarker of muscular injuries and cardiac assault. In this study, we developed a structure-switching aptamer that can be immobilized on a sensor to detect CK-MM. CK-BB was used as a counter-target to ensure the specific targeting of CK-MM. Melting-Off SELEX was employed to develop aptamers exhibiting significant structural changes on binding. The selected aptamer shows a high affinity towards CK-MM with a Kd value of 14.7 nM.

A Change-Point Method to Detect Meaningful Change in Return-to-Sport Progression in Athletes.

To explore how the change-point method can be used to analyze complex longitudinal data and detect when meaningful changes (change points) have occurred during rehabilitation. This design is a prospective single-case observational study of a football player in a professional club who sustained an acute lower-limb muscle injury during high-speed running in training. The rehabilitation program was entirely completed in the football club under the supervision of the club's medical team. Four wellness metrics and 5 running-performance metrics were collected before the injury and until the player returned to play. Data were collected over 130days. In the univariate analysis, the change points for stress, sleep, mood, and soreness were located on days 30, 47, 50, and 50, respectively. The change points for total distance, acceleration, maximum speed, deceleration, and high-speed running were located on days 32, 34, 37, 41, and 41, respectively. The multivariate analysis resulted in a single change point for the wellness metrics and running-performance metrics, on days 50 and 67, respectively. The univariate approach provided information regarding the sequence and time point of the change points. The multivariate approach provided a common change point for multiple metrics, information that would benefit clinicians to have a broad overview of the changes in the rehabilitation process. Clinicians may consider the change-point method to integrate and visualize data from multiple sources to evaluate athletes' progression along the return-to-sport continuum.

Identification and Analysis of Myogenic Progenitors In Vivo During Acute Skeletal Muscle Injury by High-Dimensional Single-Cell Mass Cytometry.

Skeletal muscle regeneration is a dynamic process driven by adult muscle stem cells and their progeny. Mostly quiescent at a steady state, adult muscle stem cells become activated upon muscle injury. Following activation, they proliferate, and most of their progeny differentiate to generate fusion-competent muscle cells while the remaining self-renews to replenish the stem cell pool. While the identity of muscle stem cells was defined more than a decade ago, based on the co-expression of cell surface markers, myogenic progenitors were identified only recently using high-dimensional single-cell approaches. Here, we present a single-cell mass cytometry (cytometry by time of flight [CyTOF]) method to analyze stem cells and progenitor cells in acute muscle injury to resolve the cellular and molecular dynamics that unfold during muscle regeneration. This approach is based on the simultaneous detection of novel cell surface markers and key myogenic transcription factors whose dynamic expression enables the identification of activated stem cells and progenitor cell populations that represent landmarks of myogenesis. Importantly, a sorting strategy based on detecting cell surface markers CD9 and CD104 is described, enabling prospective isolation of muscle stem and progenitor cells using fluorescence-activated cell sorting (FACS) for in-depth studies of their function. Muscle progenitor cells provide a critical missing link to study the control of muscle stem cell fate, identify novel therapeutic targets for muscle diseases, and develop cell therapy applications for regenerative medicine. The approach presented here can be applied to study muscle stem and progenitor cells in vivo in response to perturbations, such as pharmacological interventions targeting specific signaling pathways. It can also be used to investigate the dynamics of muscle stem and progenitor cells in animal models of muscle diseases, advancing our understanding of stem cell diseases and accelerating the development of therapies.