scholarly journals Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Stéphanie Charrin ◽  
Mathilde Latil ◽  
Sabrina Soave ◽  
Anna Polesskaya ◽  
Fabrice Chrétien ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Muscle Cell ◽  
Muscle Regeneration ◽  
Tight Control ◽  
Normal Muscle

scholarly journals TGFβ signaling curbs cell fusion and muscle regeneration

2019 ◽  
Author(s):  
Francesco Girardi ◽  
Anissa Taleb ◽  
Lorenzo Giordani ◽  
Bruno Cadot ◽  
Asiman Datye ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Muscle Cell ◽  
Transforming Growth Factor Beta ◽  
Muscle Regeneration ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Transforming Growth Factor ◽  
Actin Dynamics ◽  
Tgfβ Signaling

SummaryFusion of muscle progenitor cells is necessary for skeletal muscle development and repair. Cell fusion is a multistep process involving cell migration, adhesion, membrane remodeling and actin-nucleation pathways to generate multinucleated myotubes. While the cellular and molecular mechanisms promoting muscle cell fusion have been intensely investigated in recent years, molecular brakes restraining cell–cell fusion events to control syncytia formation have remained elusive. Here, we show that transforming growth factor beta (TGFβ) signaling is active in adult muscle cells throughout the fusion process and reduce muscle cell fusion independently of the differentiation step. In contrast, inhibition of TGFβ signaling enhances cell fusion and promotes branching between myotubes. Pharmacological modulation of the pathway in vivo perturbs muscle regeneration after injury. Exogenous addition of TGFβ protein results in a loss of muscle function while inhibition of the TGFβ pathway induces the formation of giant myofibres. Transcriptome analyses and functional assays revealed that TGFβ acts on actin dynamics and reduce cell spreading through modulation of actin-based protrusions. Together our results reveal a signaling pathway that limits mammalian myoblast fusion and add a new level of understanding to the molecular regulation of myogenesis.

The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms

2006 ◽  
Vol 290 (6) ◽  
pp. C1651-C1659 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Grace K. Pavlath
Keyword(s):  
Muscle Mass ◽  
Muscle Regeneration ◽  
Muscle Growth ◽  
Cell Activity ◽  
Hindlimb Suspension ◽  
Normal Muscle ◽  
Cox 2 ◽  
Proliferation In Vitro

Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg·kg−1·day−1) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2−/− satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.

scholarly journals R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

Cell Reports ◽  
2017 ◽  
Vol 18 (10) ◽  
pp. 2320-2330 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
C. Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Lorenzo Giordani ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cell Fusion ◽  
Muscle Cell

scholarly journals Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190

2015 ◽  
Vol 309 (7) ◽  
pp. C491-C500 ◽  
Author(s):  
Samantha Gardner ◽  
Sean M. Gross ◽  
Larry L. David ◽  
John E. Klimek ◽  
Peter Rotwein
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Cell Fusion ◽  
Muscle Cell ◽  
Map Kinases ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Myoblast Differentiation ◽  
Igf I ◽  
Muscle Biology

The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes regulated by these kinases remain poorly defined. Here we find that activity of p38α/β is important not only in early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treatment of C2 myoblasts with the promyogenic growth factor insulin-like growth factor (IGF)-I, the early block in differentiation imposed by the p38 chemical inhibitor SB202190 could be overcome. Yet, under these conditions, IGF-I could not prevent the later impairment of muscle cell fusion, as marked by the nearly complete absence of multinucleated myofibers. Removal of SB202190 from the medium of differentiating myoblasts reversed the fusion block, as multinucleated myofibers were detected several hours later and reached ∼90% of the culture within 30 h. Analysis by quantitative mass spectroscopy of proteins that changed in abundance following removal of the inhibitor revealed a cohort of upregulated muscle-enriched molecules that may be important for both myofibrillogenesis and fusion. We have thus developed a model system that allows separation of myoblast differentiation from muscle cell fusion and should be useful in identifying specific steps regulated by p38 MAP kinase-mediated signaling in myogenesis.

Short Communication: Antiretroviral Protease Inhibitors Prevent L6 Muscle Cell Fusion by Reducing Calpain Activity

2004 ◽  
Vol 20 (10) ◽  
pp. 1057-1062 ◽  
Author(s):  
Susan P. Colby-Germinario ◽  
Lorraine E. Chalifour ◽  
Anthony Antonecchia ◽  
Ralph J. Germinario
Keyword(s):  
Protease Inhibitors ◽  
Cell Fusion ◽  
Muscle Cell ◽  
Short Communication ◽  
Calpain Activity

scholarly journals Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube Maintenance

1999 ◽  
Vol 146 (4) ◽  
pp. 893-904 ◽  
Author(s):  
Isao Tachibana ◽  
Martin E. Hemler
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Fusion ◽  
Muscle Cell ◽  
C2c12 Cell ◽  
Ectopic Expression ◽  
C2c12 Cells ◽  
C2c12 Myoblast ◽  
Syncytia Formation ◽  
Transmembrane 4 Superfamily

The role of transmembrane 4 superfamily (TM4SF) proteins during muscle cell fusion has not been investigated previously. Here we show that the appearance of TM4SF protein, CD9, and the formation of CD9–β1 integrin complexes were both regulated in coordination with murine C2C12 myoblast cell differentiation. Also, anti-CD9 and anti-CD81 monoclonal antibodies substantially inhibited and delayed conversion of C2C12 cells to elongated myotubes, without affecting muscle-specific protein expression. Studies of the human myoblast-derived RD sarcoma cell line further demonstrated that TM4SF proteins have a role during muscle cell fusion. Ectopic expression of CD9 caused a four- to eightfold increase in RD cell syncytia formation, whereas anti-CD9 and anti-CD81 antibodies markedly delayed RD syncytia formation. Finally, anti-CD9 and anti-CD81 monoclonal antibodies triggered apoptotic degeneration of C2C12 cell myotubes after they were formed. In summary, TM4SF proteins such as CD9 and CD81 appear to promote muscle cell fusion and support myotube maintenance.

scholarly journals A novel isoform of MAP4 organises the paraxial microtubule array required for muscle cell differentiation

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Binyam Mogessie ◽  
Daniel Roth ◽  
Zainab Rahil ◽  
Anne Straube
Keyword(s):  
Cell Differentiation ◽  
Cell Fusion ◽  
Muscle Cell ◽  
Cell Elongation ◽  
Myogenic Differentiation ◽  
Muscle Cells ◽  
Microtubule Array ◽  
Muscle Cell Differentiation ◽  
Microtubule Transport

The microtubule cytoskeleton is critical for muscle cell differentiation and undergoes reorganisation into an array of paraxial microtubules, which serves as template for contractile sarcomere formation. In this study, we identify a previously uncharacterised isoform of microtubule-associated protein MAP4, oMAP4, as a microtubule organising factor that is crucial for myogenesis. We show that oMAP4 is expressed upon muscle cell differentiation and is the only MAP4 isoform essential for normal progression of the myogenic differentiation programme. Depletion of oMAP4 impairs cell elongation and cell–cell fusion. Most notably, oMAP4 is required for paraxial microtubule organisation in muscle cells and prevents dynein- and kinesin-driven microtubule–microtubule sliding. Purified oMAP4 aligns dynamic microtubules into antiparallel bundles that withstand motor forces in vitro. We propose a model in which the cooperation of dynein-mediated microtubule transport and oMAP4-mediated zippering of microtubules drives formation of a paraxial microtubule array that provides critical support for the polarisation and elongation of myotubes.

scholarly journals Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

2020 ◽  
Author(s):  
Hasan Abbas ◽  
Lindsey A. Olivere ◽  
Michael E. Padgett ◽  
Cameron A. Schmidt ◽  
Brian F. Gilmore ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Ischemic Injury ◽  
Limb Ischemia ◽  
Normal Muscle ◽  
Mouse Muscle ◽  
Muscle Progenitor Cells ◽  
Artery Disease

AbstractPeripheral artery disease (PAD) is nearly as common as coronary artery disease, but few effective treatments exist, and it is associated with significant morbidity and mortality. Although PAD studies have focused on the vascular response to ischemia, skeletal muscle cells play a critically important role in determining the phenotypic manifestation of PAD. Here, we demonstrate that genetic ablation of Pax7+ muscle progenitor cells (MPCs, or satellite cells) in a murine model of hind limb ischemia (HLI) resulted in a complete absence of normal muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to ischemic muscle of control mice (Pax7WT), the ischemic limb of Pax7-deficient mice (Pax7Δ) was unable to generate significant force 7- or 28-days after HLI in ex vivo force measurement studies. A dramatic increase in adipose infiltration was observed 28 days after HLI in Pax7Δ mice, which replaced functional muscle. To investigate the mechanism of this adipogenic change, mice with inhibition of fibro/adipogenic precursors (FAPs), another pool of MPCs, were subjected to HLI. Inhibition of FAPs decreased muscle adipose fat but increased fibrosis. MPCs cultured from mouse muscle tissue failed to form myotubes in vitro following depletion of satellite cells in vivo, and they displayed an increased propensity to differentiate into fat in adipogenic medium. Importantly, this phenotype was recapitulated in patients with critical limb ischemia (CLI), the most severe form of PAD. Skeletal muscle samples from CLI patients demonstrated an increase in adipose deposition in more ischemic regions of muscle, which corresponded with a decrease in the number of satellite cells in those regions. Collectively, these data demonstrate that Pax7+ MPCs are required for normal muscle regeneration after ischemic injury, and they suggest that targeting muscle regeneration may be an important therapeutic approach to prevent muscle degeneration in PAD.

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