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Ryanodine receptor RyR1-mediated elevation of Ca2+ concentration is required for the late stage of myogenic differentiation and fusion.

BACKGROUND: Cytosolic Ca2+ plays vital roles in myogenesis and muscle development. As a major Ca2+ release channel of endoplasmic reticulum (ER), ryanodine receptor 1 (RyR1) key mutations are main causes of severe congenital myopathies. The role of RyR1 in myogenic differentiation has attracted intense research interest but remains unclear. RESULTS: In the present study, both RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts were employed to explore the role of RyR1 in myogenic differentiation, myotube formation as well as the potential mechanism of RyR1-related myopathie…

A novel catheter system for percutaneous intracoronary artery cardiomyoplasty.

BACKGROUND: Current medical and invasive treatment strategies are often found to be inadequate to treat patients with acute myocardial infar … catheter that delivers the injection needle catheter into the target lesion. We harvested skeletal myoblasts from Yorkshire swine (n = 8; 50-60 kg), expanded them in culture and labeled them with a fluorescent cell-linker kit. The myoblasts (106 cells), along with green dye, were injected into the normal heart of swine using this novel system. Histological …

Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1.

The mammalian target of rapamycin (mTOR), a critical modulator of cell growth, acts to integrate signals from hormones, nutrients, and growt … cally induced following acute dexamethasone treatment both in rat skeletal muscle in vivo and in L6 myoblasts in culture. In L6 myoblasts, the effect of the drug on mTOR signaling is efficiently blunted in the presence of REDD1 RNA interference oligonucleotides. Moreover, the dexamethasone-induced assembly of the mTOR regulatory complex Tuberin. Hamartin is …

Caveolin-3 regulates the activity of Ca2+/calmodulin-dependent protein kinase II in C2C12 cells.

Caveolins, encoded by the Cav gene family, are the main components of caveolae. Caveolin-3 (Cav3) is specifically expressed in muscle cells. … Cav3 expression levels or localization influences muscle cell functions. Here, we used mouse C2C12 myoblasts in which Cav3 expression was suppressed with short hairpin RNA and found that Cav3 suppression impaired myotube differentiation without affecting the expression of MyoD and Myog. We also observed an increase of intracellular Ca2+ levels, total calpa …

Антивоспламенительный макропхаж-сухие экзосомы, модифицированные с помощью самоантигенных пептидов для лечения экспериментального аутоиммунного энцефаломелита.

Текущее лечение аутоиммунных заболеваний часто сопряжено с широкодействующими иммунодепрессантами, которые сопряжены с такими рисками, как инфекционные заболевания и болезни. В ходе этого исследования изучается вопрос о том, могут ли экзосомы, полученные из антивоспалительных макрофаг (АЭ) и украшенные миэлином олигодендроцитом гликопротеином (МОГ) пептидом (АЭ/М), способствовать иммунной терпимости при аутоиммунных заболеваниях. Экспериментальный аутоиммунный энцефаломиэлит (EAE), модель мыши для множественных склерозов, служит моделью аутоиммунных заболеваний. Экзосомы, получаемые из миоблас

Совпадение в аннотации оригинала
Current treatments for autoimmune diseases often involve broad-acting immunosuppressants, which carry risks such as infections and malignanc … a mouse model for multiple sclerosis, serves as the autoimmune disease model. Exosomes derived from myoblasts or fibroblasts are also modified with MOG peptides for comparison. Unlike their myoblast or fibroblast counterparts, exosomes from anti-inflammatory macrophages demonstrate a targeted capacity toward antigen-presenting cells. Moreover, AE/M uniquely …

Isolation and Characterization of Compounds from Glycyrrhiza uralensis as Therapeutic Agents for the Muscle Disorders.

Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl a

Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle myogenesis.

Cellulose nanowhiskers (CNWs) are high-aspect-ratio rod-like nanoparticles prepared via partial hydrolysis of cellulose. For the first time, CNWs have been extracted from the marine invertebrate Ascidiella aspersa, yielding animal-derived CNWs with particularly small diameters of only a few nanometres. Oriented surfaces of adsorbed CNWs were prepared using a flexible and facile spin-coating method, allowing the modulation of CNW adsorption and relative orientation. Due to the shape and nanoscale dimensions of the CNWs, C2C12 myoblasts adopted increasingly oriented morphologies in response to m…

Myoglobin and the regulation of mitochondrial respiratory chain complex IV.

KEY POINTS: Mitochondrial respiration is regulated by multiple elaborate mechanisms. It has been shown that muscle specific O2 binding protein, Myoglobin (Mb), is localized in mitochondria and interacts with respiratory chain complex IV, suggesting that Mb could be a factor that regulates mitochondrial respiration. Here, we demonstrate that muscle mitochondrial respiration is improved by Mb overexpression via up-regulation of complex IV activity in cultured myoblasts; in contrast, suppression of Mb expression induces a decrease in complex IV activity and mitochondrial respiration compared with…

Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures.

OBJECTIVES: We evaluated whether human adult bone marrow-derived mesenchymal stem cells (hMSCs) could repair an experimentally induced conduction block in cardiomyocyte cultures. BACKGROUND: Autologous stem cell therapy is a novel treatment option for patients with heart disease. However, detailed electrophysiological characterization of hMSCs is still lacking. METHODS: Neonatal rat cardiomyocytes were seeded on multi-electrode arrays. After 48 h, abrasion of a 200- to 450-microm-wide channel caused conduction block. Next, we applied adult hMSCs (hMSC group, n = 8), human skeletal myoblasts …

Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition.

Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscl…

Muscle regeneration induced by snake venom. A histological and histochemical study.

This report describes the regeneration pattern of anterior tibial muscle of the rat after the inoculation of the snake venom of Bothrops jararacussu. The results show that this regeneration pattern is rather similar to the pattern described in other experimental models. Three days after the injection, three differentiated areas are established: a peripheric one of surviving fibres, a second one called myogenic area, and the last one, more internal, made of necrotic fibres that are phagocytized by macrophages. The surface of the surviving muscle fibres has myoblasts sticking to it and five days…

Enhanced Expression of IL32 mRNA in Skeletal Muscles in the Context of Head and Neck Carcinomas.

BACKGROUND: Cancer-related sarcopenia (CRS) is a significant complication of head and neck carcinoma (HNC), characterised by muscle degeneration and poor clinical outcomes. Although various dietary and therapeutic interventions have been explored, most of them remain empirical, and the molecular mechanisms underlying CRS are not yet fully understood. METHODS: Transcription profiles of muscle fragments from 29 HNC patients and 8 control donors were analysed by bulk RNA sequencing (6/29 and 3/8) and/or RT-qPCR (29/29 and 5/8). In parallel, differentiating human myoblasts (AB1190) were subjected…

The dose-response effects of flurbiprofen, indomethacin, ibuprofen, and naproxen on primary skeletal muscle cells.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, flurbiprofen, naproxen sodium, and indomethacin are commonly employed for their pain-relieving and inflammation-reducing qualities. NSAIDs work by blocking COX-1 and/or COX-2, enzymes which play roles in inflammation, fever, and pain. The main difference among NSAIDs lies in their affinity to these enzymes, which in turn, influences prostaglandin secretion, and skeletal muscle growth and regeneration. The current study investigated the effects of NSAIDs on human skeletal muscle cells, focusing on myoblast proliferation,

Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF-2α misexpression.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) refers to a three-dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was implicated to regulate myogenesis. This study aims to investigate the association between myogenesis/muscle toning and HIF-αs activity in the pathogenesis of AIS. METHODS: HIF-αs expression was examined by enzyme-linked immunosorbent assay and western blot in paraspinal myoblasts isolated from 18 sub…

Consequences of GMPPB deficiency for neuromuscular development and maintenance.

Guanosine diphosphate-mannose pyrophosphorylase B (GMPPB) catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, which is r … e of GMPPB in vitro. Thereby, we found that the siRNA-mediated knockdown of Gmppb in either primary myoblasts or the myoblast cell line C2C12 impaired myoblast differentiation and resulted in myotube degeneration. siRNA-mediated knockdown of Gmppb also impaired the neuron-like differentiation of N2A cells. Taken together, our data highlight the essential ro …

Antiapoptotic Protein FAIM2 is targeted by miR-3202, and DUX4 via TRIM21, leading to cell death and defective myogenesis.

Inappropriate expression of DUX4, a transcription factor that induces cell death at high levels of expression and impairs myoblast differentiation at low levels of expression, leads to the development of facioscapulohumeral muscular dystrophy (FSHD), however, the pathological mechanisms downstream of DUX4 responsible for muscle loss are poorly defined. We performed a screen of 1972 miR inhibitors for their ability to interfere with DUX4-induced cell death of human immortalized myoblasts. The most potent hit identified by the screen, miR-3202, is known to target the antiapoptotic protein FAIM2.…

Caveolin 3 suppresses phosphorylation-dependent activation of sarcolemmal nNOS.

Mutations of the caveolin 3 gene cause autosomal dominant limb-girdle muscular dystrophy (LGMD)1C. In mice, overexpression of mutant caveolin 3 leads to loss of caveolin 3 and results in myofiber hypotrophy in association with activation of neuronal nitric oxide synthase (nNOS) at the sarcolemma. Here, we show that caveolin 3 directly bound to nNOS and suppressed its phosphorylation-dependent activation at a specific residue, Ser1412 in the nicotinamide adenine dinucleotide phosphate (NADPH)-flavin adenine dinucleotide (FAD) module near the C-terminus of the reduction domain, in vitro. Constit

Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs.

AUF1 promotes rapid decay of mRNAs containing 3' untranslated region (3'UTR) AU-rich elements (AREs). AUF1 depletion in mice accelerates muscle loss and causes limb girdle muscular dystrophy. Here, we demonstrate that the selective, targeted degradation by AUF1 of key muscle stem cell fate-determining checkpoint mRNAs regulates each stage of muscle development and regeneration by reprogramming each myogenic stage. Skeletal muscle stem (satellite) cell explants show that Auf1 transcription is activated with satellite cell activation by stem cell regulatory factor CTCF. AUF1 then targets checkpo

Distinct patterns of MMP-9 and MMP-2 activity in slow and fast twitch skeletal muscle regeneration in vivo.

Skeletal muscles exhibit great plasticity and an ability to reconstruct in response to injury. However, the repair process is often ineffici … is and increased MMP-2 activity at the reconstruction phase. Moreover, satellite cells (mononuclear myoblasts) derived from Soleus and EDL muscles showed no differences in localization or activity of MMP-9 and MMP-2 during proliferation and differentiation in vitro. MMP-9 activity was present during all stages of myoblast differentiation, whereas MMP-2 acti …

High-throughput screening identifies bazedoxifene as a potential therapeutic for dysferlin-deficient limb girdle muscular dystrophy.

BACKGROUND AND PURPOSE: Limb-girdle muscular dystrophy R2 (LGMD R2) is a rare genetic disorder characterised by progressive weakness and was … monitor the expression and reallocation of aggregated mutant dysferlin (DYSFL1341P) in immortalised myoblasts. After screening 2239 clinically approved drugs and bioactive compounds, the ability of the more promising candidates to improve cell survival following hypo-osmotic shock was assessed. Their protective effects were evaluated on immortalised myoblas …