Skeletal Muscle最新文献

{"title":"Alternative splicing diversifies the skeletal muscle transcriptome during prolonged spaceflight","authors":"Mason Henrich, Pin Ha, Yuanyuan Wang, K. Ting, L. Stodieck, C. Soo, John S. Adams, R. Chun","doi":"10.1186/s13395-022-00294-9","DOIUrl":"https://doi.org/10.1186/s13395-022-00294-9","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44565760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth differentiation factor 11 induces skeletal muscle atrophy via a STAT3-dependent mechanism in pulmonary arterial hypertension","authors":"Xiang, Guiling, Ying, Kelu, Jiang, Pan, Jia, Mengping, Sun, Yipeng, Li, Shanqun, Wu, Xiaodan, Hao, Shengyu","doi":"10.1186/s13395-022-00292-x","DOIUrl":"https://doi.org/10.1186/s13395-022-00292-x","url":null,"abstract":"Skeletal muscle wasting is a clinically remarkable phenotypic feature of pulmonary arterial hypertension (PAH) that increases the risk of mortality. Growth differentiation factor 11 (GDF11), centrally involved in PAH pathogenesis, has an inhibitory effect on skeletal muscle growth in other conditions. However, whether GDF11 is involved in the pathogenesis of skeletal muscle wasting in PAH remains unknown. We showed that serum GDF11 levels in patients were increased following PAH. Skeletal muscle wasting in the MCT-treated PAH model is accompanied by an increase in circulating GDF11 levels and local catabolic markers (Fbx32, Trim63, Foxo1, and protease activity). In vitro GDF11 activated phosphorylation of STAT3. Antagonizing STAT3, with Stattic, in vitro and in vivo, could partially reverse proteolytic pathways including STAT3/socs3 and iNOS/NO in GDF11-meditated muscle wasting. Our findings demonstrate that GDF11 contributes to muscle wasting and the inhibition of its downstream molecule STAT3 shows promise as a therapeutic intervention by which muscle atrophy may be directly prevented in PAH.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"159 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Notch signaling network in muscle stem cells during development, homeostasis, and disease","authors":"Gioftsidi, Stamatia, Relaix, Frederic, Mourikis, Philippos","doi":"10.1186/s13395-022-00293-w","DOIUrl":"https://doi.org/10.1186/s13395-022-00293-w","url":null,"abstract":"Skeletal muscle stem cells have a central role in muscle growth and regeneration. They reside as quiescent cells in resting muscle and in response to damage they transiently amplify and fuse to produce new myofibers or self-renew to replenish the stem cell pool. A signaling pathway that is critical in the regulation of all these processes is Notch. Despite the major differences in the anatomical and cellular niches between the embryonic myotome, the adult sarcolemma/basement-membrane interphase, and the regenerating muscle, Notch signaling has evolved to support the context-specific requirements of the muscle cells. In this review, we discuss the diverse ways by which Notch signaling factors and other modifying partners are operating during the lifetime of muscle stem cells to establish an adaptive dynamic network.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"159 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endurance exercise attenuates juvenile irradiation-induced skeletal muscle functional decline and mitochondrial stress.","authors":"Thomas N O'Connor, Jacob G Kallenbach, Haley M Orciuoli, Nicole D Paris, John F Bachman, Carl J Johnston, Eric Hernady, Jacqueline P Williams, Robert T Dirksen, Joe V Chakkalakal","doi":"10.1186/s13395-022-00291-y","DOIUrl":"10.1186/s13395-022-00291-y","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is commonly used to treat childhood cancers and can have adverse effects on muscle function, but the underlying mechanisms have yet to be fully elucidated. We hypothesized that endurance exercise following radiation treatment would improve skeletal muscle function.</p><p><strong>Methods: </strong>We utilized the Small Animal Radiation Research Platform (SARRP) to irradiate juvenile male mice with a clinically relevant fractionated dose of 3× (every other day over 5 days) 8.2 Gy X-ray irradiation locally from the knee to footpad region of the right hindlimb. Mice were then singly housed for 1 month in cages equipped with either locked or free-spinning voluntary running wheels. Ex vivo muscle contractile function, RT-qPCR analyses, resting cytosolic and sarcoplasmic reticulum (SR) store Ca²⁺ levels, mitochondrial reactive oxygen species levels (MitoSOX), and immunohistochemical and biochemical analyses of muscle samples were conducted to assess the muscle pathology and the relative therapeutic impact of voluntary wheel running (VWR).</p><p><strong>Results: </strong>Irradiation reduced fast-twitch extensor digitorum longus (EDL) muscle-specific force by 27% compared to that of non-irradiated mice, while VWR post-irradiation improved muscle-specific force by 37%. Radiation treatment similarly reduced slow-twitch soleus muscle-specific force by 14% compared to that of non-irradiated mice, while VWR post-irradiation improved specific force by 18%. We assessed intracellular Ca²⁺ regulation, oxidative stress, and mitochondrial homeostasis as potential mechanisms of radiation-induced pathology and exercise-mediated rescue. We found a significant reduction in resting cytosolic Ca²⁺ concentration following irradiation in sedentary mice. Intriguingly, however, SR Ca²⁺ store content was increased in myofibers from irradiated mice post-VWR compared to mice that remained sedentary. We observed a 73% elevation in the overall protein oxidization in muscle post-irradiation, while VWR reduced protein nitrosylation by 35% and mitochondrial reactive oxygen species (ROS) production by 50%. Finally, we found that VWR significantly increased the expression of PGC1α at both the transcript and protein levels, consistent with an exercise-dependent increase in mitochondrial biogenesis.</p><p><strong>Conclusions: </strong>Juvenile irradiation stunted muscle development, disrupted proper Ca²⁺ handling, damaged mitochondria, and increased oxidative and nitrosative stress, paralleling significant deficits in muscle force production. Exercise mitigated aberrant Ca²⁺ handling, mitochondrial homeostasis, and increased oxidative and nitrosative stress in a manner that correlated with improved skeletal muscle function after radiation.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"12 1","pages":"8"},"PeriodicalIF":4.9,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional replacement of myostatin with GDF-11 in the germline of mice","authors":"Lee, Se-Jin, Lehar, Adam, Rydzik, Renata, Youngstrom, Daniel W., Bhasin, Shalender, Liu, Yewei, Germain-Lee, Emily L.","doi":"10.1186/s13395-022-00290-z","DOIUrl":"https://doi.org/10.1186/s13395-022-00290-z","url":null,"abstract":"Myostatin (MSTN) is a transforming growth factor-ß superfamily member that acts as a major regulator of skeletal muscle mass. GDF-11, which is highly related to MSTN, plays multiple roles during embryonic development, including regulating development of the axial skeleton, kidneys, nervous system, and pancreas. As MSTN and GDF-11 share a high degree of amino acid sequence identity, behave virtually identically in cell culture assays, and utilize similar regulatory and signaling components, a critical question is whether their distinct biological functions result from inherent differences in their abilities to interact with specific regulatory and signaling components or whether their distinct biological functions mainly reflect their differing temporal and spatial patterns of expression. We generated and characterized mice in which we precisely replaced in the germline the portion of the Mstn gene encoding the mature C-terminal peptide with the corresponding region of Gdf11. In mice homozygous for the knock-in allele, all of the circulating MSTN protein was replaced with GDF-11, resulting in ~ 30–40-fold increased levels of circulating GDF-11. Male mice homozygous for the knock-in allele had slightly decreased muscle weights, slightly increased weight gain in response to a high-fat diet, slightly increased plasma cholesterol and HDL levels, and significantly decreased bone density and bone mass, whereas female mice were mostly unaffected. GDF-11 appears to be capable of nearly completely functionally replacing MSTN in the control of muscle mass. The developmental and physiological consequences of replacing MSTN with GDF-11 are strikingly limited.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"162 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of chronic intermittent hypoxia (CIH) on neuromuscular junctions and mitochondria in slow- and fast-twitch skeletal muscles of mice-the role of iNOS.","authors":"L I Bannow,&nbsp;G A Bonaterra,&nbsp;M Bertoune,&nbsp;S Maus,&nbsp;R Schulz,&nbsp;N Weissmann,&nbsp;S Kraut,&nbsp;R Kinscherf,&nbsp;W Hildebrandt","doi":"10.1186/s13395-022-00288-7","DOIUrl":"https://doi.org/10.1186/s13395-022-00288-7","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) imposes vascular and metabolic risks through chronic intermittent hypoxia (CIH) and impairs skeletal muscle performance. As studies addressing limb muscles are rare, the reasons for the lower exercise capacity are unknown. We hypothesize that CIH-related morphological alterations in neuromuscular junctions (NMJ) and mitochondrial integrity might be the cause of functional disorders in skeletal muscles.</p><p><strong>Methods: </strong>Mice were kept under 6 weeks of CIH (alternating 7% and 21% O₂ fractions every 30 s, 8 h/day, 5 days/week) compared to normoxia (NOX). Analyses included neuromuscular junctions (NMJ) postsynaptic morphology and integrity, fiber cross-sectional area (CSA) and composition (ATPase), mitochondrial ultrastructure (transmission-electron-microscopy), and relevant transcripts (RT-qPCR). Besides wildtype (WT), we included inducible nitric oxide synthase knockout mice (iNOS^-/-) to evaluate whether iNOS is protective or risk-mediating.</p><p><strong>Results: </strong>In WT soleus muscle, CIH vs. NOX reduced NMJ size (- 37.0%, p < 0.001) and length (- 25.0%, p < 0.05) together with fiber CSA of type IIa fibers (- 14%, p < 0.05) and increased centronucleated fiber fraction (p < 0.001). Moreover, CIH vs. NOX increased the fraction of damaged mitochondria (1.8-fold, p < 0.001). Compared to WT, iNOS^-/- similarly decreased NMJ area and length with NOX (- 55%, p < 0.001 and - 33%, p < 0.05, respectively) or with CIH (- 37%, p < 0.05 and - 29%, p < 0.05), however, prompted no fiber atrophy. Moreover, increased fractions of damaged (2.1-fold, p < 0.001) or swollen (> 6-fold, p < 0.001) mitochondria were observed with iNOS^-/- vs. WT under NOX and similarly under CIH. Both, CIH- and iNOS^-/- massively upregulated suppressor-of-cytokine-signaling-3 (SOCS3) > 10-fold without changes in IL6 mRNA expression. Furthermore, inflammatory markers like CD68 (macrophages) and IL1β were significantly lower in CIH vs. NOX. None of these morphological alterations with CIH- or iNOS^-/- were detected in the gastrocnemius muscle. Notably, iNOS expression was undetectable in WT muscle, unlike the liver, where it was massively decreased with CIH.</p><p><strong>Conclusion: </strong>CIH leads to NMJ and mitochondrial damage associated with fiber atrophy/centronucleation selectively in slow-twitch muscle of WT. This effect is largely mimicked by iNOS^-/- at NOX (except for atrophy). Both conditions involve massive SOCS3 upregulation likely through denervation without Il6 upregulation but accompanied by a decrease of macrophage density especially next to denervated endplates. In the absence of muscular iNOS expression in WT, this damage may arise from extramuscular, e.g., motoneuronal iNOS deficiency (through CIH or knockout) awaiting functional evaluation.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"6"},"PeriodicalIF":4.9,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39609266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle stem cell adaptations to cellular and environmental stress.","authors":"Maria Vittoria Gugliuzza,&nbsp;Colin Crist","doi":"10.1186/s13395-022-00289-6","DOIUrl":"https://doi.org/10.1186/s13395-022-00289-6","url":null,"abstract":"<p><strong>Background: </strong>Lifelong regeneration of the skeletal muscle is dependent on a rare population of resident skeletal muscle stem cells, also named 'satellite cells' for their anatomical position on the outside of the myofibre and underneath the basal lamina. Muscle stem cells maintain prolonged quiescence, but activate the myogenic programme and the cell cycle in response to injury to expand a population of myogenic progenitors required to regenerate muscle. The skeletal muscle does not regenerate in the absence of muscle stem cells.</p><p><strong>Main body: </strong>The notion that lifelong regeneration of the muscle is dependent on a rare, non-redundant population of stem cells seems contradictory to accumulating evidence that muscle stem cells have activated multiple stress response pathways. For example, muscle stem cell quiescence is mediated in part by the eIF2α arm of the integrated stress response and by negative regulators of mTORC1, two translational control pathways that downregulate protein synthesis in response to stress. Muscle stem cells also activate pathways to protect against DNA damage, heat shock, and environmental stress. Here, we review accumulating evidence that muscle stem cells encounter stress during their prolonged quiescence and their activation. While stress response pathways are classically described to be bimodal whereby a threshold dictates cell survival versus cell death responses to stress, we review evidence that muscle stem cells additionally respond to stress by spontaneous activation and fusion to myofibres.</p><p><strong>Conclusion: </strong>We propose a cellular stress test model whereby the prolonged state of quiescence and the microenvironment serve as selective pressures to maintain muscle stem cell fitness, to safeguard the lifelong regeneration of the muscle. Fit muscle stem cells that maintain robust stress responses are permitted to maintain the muscle stem cell pool. Unfit muscle stem cells are depleted from the pool first by spontaneous activation, or in the case of severe stress, by activating cell death or senescence pathways.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"5"},"PeriodicalIF":4.9,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic signatures for the longitudinal reduction of muscle strength over 10 years.","authors":"Salem Werdyani,&nbsp;Dawn Aitken,&nbsp;Zhiwei Gao,&nbsp;Ming Liu,&nbsp;Edward W Randell,&nbsp;Proton Rahman,&nbsp;Graeme Jones,&nbsp;Guangju Zhai","doi":"10.1186/s13395-022-00286-9","DOIUrl":"https://doi.org/10.1186/s13395-022-00286-9","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscles are essential components of the neuromuscular skeletal system that have an integral role in the structure and function of the synovial joints which are often affected by osteoarthritis (OA). The aim of this study was to identify the baseline metabolomic signatures for the longitudinal reduction of muscle strength over 10 years in the well-established community-based Tasmanian Older Adult Cohort (TASOAC).</p><p><strong>Methods: </strong>Study participants were 50-79 year old individuals from the TASOAC. Hand grip, knee extension, and leg strength were measured at baseline, 2.6-, 5-, and 10-year follow-up points. Fasting serum samples were collected at 2.6-year follow-up point, and metabolomic profiling was performed using the TMIC Prime Metabolomics Profiling Assay. Generalized linear mixed effects model was used to identify metabolites that were associated with the reduction in muscle strength over 10 years after controlling for age, sex, and BMI. Significance level was defined at α=0.0004 after correction of multiple testing of 129 metabolites with Bonferroni method. Further, a genome-wide association study (GWAS) analysis was performed to explore if genetic factors account for the association between the identified metabolomic markers and the longitudinal reduction of muscle strength over 10 years.</p><p><strong>Results: </strong>A total of 409 older adults (50% of them females) were included. The mean age was 60.93±6.50 years, and mean BMI was 27.12±4.18 kg/m² at baseline. Muscle strength declined by 0.09 psi, 0.02 kg, and 2.57 kg per year for hand grip, knee extension, and leg strength, respectively. Among the 143 metabolites measured, 129 passed the quality checks and were included in the analysis. We found that the elevated blood level of asymmetric dimethylarginine (ADMA) was associated with the reduction in hand grip (p=0.0003) and knee extension strength (p=0.008) over 10 years. GWAS analysis found that a SNP rs1125718 adjacent to WISP1gene was associated with ADMA levels (p=4.39*10^-8). Further, we found that the increased serum concentration of uric acid was significantly associated with the decline in leg strength over 10 years (p=0.0001).</p><p><strong>Conclusion: </strong>Our results demonstrated that elevated serum ADMA and uric acid at baseline were associated with age-dependent muscle strength reduction. They might be novel targets to prevent muscle strength loss over time.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"4"},"PeriodicalIF":4.9,"publicationDate":"2022-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39897356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel γ-sarcoglycan interactors in murine muscle membranes.","authors":"Tara C Smith,&nbsp;Georgios Vasilakos,&nbsp;Scott A Shaffer,&nbsp;Jason M Puglise,&nbsp;Chih-Hsuan Chou,&nbsp;Elisabeth R Barton,&nbsp;Elizabeth J Luna","doi":"10.1186/s13395-021-00285-2","DOIUrl":"https://doi.org/10.1186/s13395-021-00285-2","url":null,"abstract":"<p><strong>Background: </strong>The sarcoglycan complex (SC) is part of a network that links the striated muscle cytoskeleton to the basal lamina across the sarcolemma. The SC coordinates changes in phosphorylation and Ca⁺⁺-flux during mechanical deformation, and these processes are disrupted with loss-of-function mutations in gamma-sarcoglycan (Sgcg) that cause Limb girdle muscular dystrophy 2C/R5.</p><p><strong>Methods: </strong>To gain insight into how the SC mediates mechano-signaling in muscle, we utilized LC-MS/MS proteomics of SC-associated proteins in immunoprecipitates from enriched sarcolemmal fractions. Criteria for inclusion were co-immunoprecipitation with anti-Sgcg from C57BL/6 control muscle and under-representation in parallel experiments with Sgcg-null muscle and with non-specific IgG. Validation of interaction was performed in co-expression experiments in human RH30 rhabdomyosarcoma cells.</p><p><strong>Results: </strong>We identified 19 candidates as direct or indirect interactors for Sgcg, including the other 3 SC proteins. Novel potential interactors included protein-phosphatase-1-catalytic-subunit-beta (Ppp1cb, PP1b) and Na⁺-K⁺-Cl^--co-transporter NKCC1 (SLC12A2). NKCC1 co-localized with Sgcg after co-expression in human RH30 rhabdomyosarcoma cells, and its cytosolic domains depleted Sgcg from cell lysates upon immunoprecipitation and co-localized with Sgcg after detergent permeabilization. NKCC1 localized in proximity to the dystrophin complex at costameres in vivo. Bumetanide inhibition of NKCC1 cotransporter activity in isolated muscles reduced SC-dependent, strain-induced increases in phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). In silico analysis suggests that candidate SC interactors may cross-talk with survival signaling pathways, including p53, estrogen receptor, and TRIM25.</p><p><strong>Conclusions: </strong>Results support that NKCC1 is a new SC-associated signaling protein. Moreover, the identities of other candidate SC interactors suggest ways by which the SC and NKCC1, along with other Sgcg interactors such as the membrane-cytoskeleton linker archvillin, may regulate kinase- and Ca⁺⁺-mediated survival signaling in skeletal muscle.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"2"},"PeriodicalIF":4.9,"publicationDate":"2022-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39711006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting report: the 2021 FSHD International Research Congress.","authors":"Sujatha Jagannathan,&nbsp;Jessica C de Greef,&nbsp;Lawrence J Hayward,&nbsp;Kyoko Yokomori,&nbsp;Davide Gabellini,&nbsp;Karlien Mul,&nbsp;Sabrina Sacconi,&nbsp;Jamshid Arjomand,&nbsp;June Kinoshita,&nbsp;Scott Q Harper","doi":"10.1186/s13395-022-00287-8","DOIUrl":"https://doi.org/10.1186/s13395-022-00287-8","url":null,"abstract":"<p><p>Facioscapulohumeral muscular dystrophy (FSHD) is the second most common genetic myopathy, characterized by slowly progressing and highly heterogeneous muscle wasting with a typical onset in the late teens/early adulthood [1]. Although the etiology of the disease for both FSHD type 1 and type 2 has been attributed to gain-of-toxic function stemming from aberrant DUX4 expression, the exact pathogenic mechanisms involved in muscle wasting have yet to be elucidated [2-4]. The 2021 FSHD International Research Congress, held virtually on June 24-25, convened over 350 researchers and clinicians to share the most recent advances in the understanding of the disease mechanism, discuss the proliferation of interventional strategies and refinement of clinical outcome measures, including results from the ReDUX4 trial, a phase 2b clinical trial of losmapimod in FSHD [NCT04003974].</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"1"},"PeriodicalIF":4.9,"publicationDate":"2022-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}