Enhanced expression of mouse c-ski accompanies terminal skeletal muscle differentiation in vivo and in vitro

AbstractDystrophies are characterized by progressive skeletal muscle degeneration and weakness as consequence of their molecular abnormalities. Thus, new drugs for restoring skeletal muscle deterioration are critically needed. To identify new and alternative compounds with a functional role in skeletal muscle myogenesis, we screened a library of pharmacologically active compounds and selected the small molecule 6-bromoindirubin-3′-oxime (BIO) as an inhibitor of myoblast proliferation. Using C2C12 cells, we examined BIO’s effect during myoblast proliferation and differentiation showing that BIO treatment promotes transition from cell proliferation to myogenic differentiation through the arrest of cell cycle. Here, we show that BIO is able to promote myogenic differentiation in damaged myotubes in-vitro by enriching the population of newly formed skeletal muscle myotubes. Moreover, in-vivo experiments in CTX-damaged TA muscle confirmed the pro-differentiation capability of BIO as shown by the increasing of the percentage of myofibers with centralized nuclei as well as by the increasing of myofibers number. Additionally, we have identified a strong correlation of miR-206 with BIO treatment both in-vitro and in-vivo: the enhanced expression of miR-206 was observed in-vitro in BIO-treated proliferating myoblasts, miR-206 restored expression was observed in a forced miR-206 silencing conditions antagomiR-mediated upon BIO treatment, and in-vivo in CTX-injured muscles miR-206 enhanced expression was observed upon BIO treatment. Taken together, our results highlight the capacity of BIO to act as a positive modulator of skeletal muscle differentiation in-vitro and in-vivo opening up a new perspective for novel therapeutic targets to correct skeletal muscle defects.

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Regulation of skeletal muscle differentiation in fibroblasts by exogenous MyoD gene in vitro and in vivo

Molecular and Cellular Biochemistry ◽

10.1007/s11010-007-9446-1 ◽

2007 ◽

Vol 302 (1-2) ◽

pp. 233-239 ◽

Cited By ~ 6

Author(s):

Rui-feng Qin ◽

Tian-qiu Mao ◽

Xiao-ming Gu ◽

Kai-jing Hu ◽

Yan-pu Liu ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Differentiation ◽

Skeletal Muscle Differentiation ◽

Myod Gene

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SWELL1-LRRC8 complex regulates skeletal muscle cell size, intracellular signalling, adiposity and glucose metabolism

10.1101/2020.06.04.134213 ◽

2020 ◽

Author(s):

Ashutosh Kumar ◽

Litao Xie ◽

Chau My Ta ◽

Antentor J. Hinton ◽

Susheel K. Gunasekar ◽

...

Keyword(s):

Skeletal Muscle ◽

Ex Vivo ◽

Anion Channel ◽

Muscle Differentiation ◽

Mtor Signaling ◽

Skeletal Muscle Differentiation ◽

Skeletal Myofiber ◽

Cellular Oxygen

AbstractMaintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism, however the molecular mechanosensor remains unknown. Here, we show that SWELL1 (LRRC8a) functionally encodes a swell-activated anion channel that regulates PI3K-AKT, ERK1/2, mTOR signaling, muscle differentiation, myoblast fusion, cellular oxygen consumption, and glycolysis in skeletal muscle cells. SWELL1 over-expression in SWELL1 KO myotubes boosts PI3K-AKT-mTOR signaling to supra-normal levels and fully rescues myotube formation. Skeletal muscle targeted SWELL1 KO mice have smaller myofibers, generate less force ex vivo, and exhibit reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet, compared to WT mice. These results reveal that the SWELL1-LRRC8 complex regulates insulin-PI3K-AKT-mTOR signalling in skeletal muscle to influence skeletal muscle differentiation in vitro and skeletal myofiber size, muscle function, adiposity and systemic metabolism in vivo.

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SWELL1 regulates skeletal muscle cell size, intracellular signaling, adiposity and glucose metabolism

eLife ◽

10.7554/elife.58941 ◽

2020 ◽

Vol 9 ◽

Author(s):

Ashutosh Kumar ◽

Litao Xie ◽

Chau My Ta ◽

Antentor O Hinton ◽

Susheel K Gunasekar ◽

...

Keyword(s):

Skeletal Muscle ◽

Intracellular Signaling ◽

Ex Vivo ◽

Anion Channel ◽

Muscle Differentiation ◽

Mtor Signaling ◽

Skeletal Muscle Differentiation ◽

Skeletal Myofiber

Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism; however, the molecular mechanosensor remains unknown. Here, we show that SWELL1 (Lrrc8a) functionally encodes a swell-activated anion channel that regulates PI3K-AKT, ERK1/2, mTOR signaling, muscle differentiation, myoblast fusion, cellular oxygen consumption, and glycolysis in skeletal muscle cells. LRRC8A over-expression in Lrrc8a KO myotubes boosts PI3K-AKT-mTOR signaling to supra-normal levels and fully rescues myotube formation. Skeletal muscle-targeted Lrrc8a KO mice have smaller myofibers, generate less force ex vivo, and exhibit reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet, compared to wild-type (WT) mice. These results reveal that the LRRC8 complex regulates insulin-PI3K-AKT-mTOR signaling in skeletal muscle to influence skeletal muscle differentiation in vitro and skeletal myofiber size, muscle function, adiposity and systemic metabolism in vivo.

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Bigbelly seahorse (Hippocampus abdominalis)-derived peptides enhance skeletal muscle differentiation and endurance performance via activated P38MAPK/AKT signalling pathway: An in vitro and in vivo analysis

Journal of Functional Foods ◽

10.1016/j.jff.2018.10.018 ◽

2019 ◽

Vol 52 ◽

pp. 147-155 ◽

Cited By ~ 3

Author(s):

Karthika Muthuramalingam ◽

Seo-Young Kim ◽

Youngmee Kim ◽

Hyun-Soo Kim ◽

You-Jin Jeon ◽

...

Keyword(s):

Skeletal Muscle ◽

Endurance Performance ◽

Muscle Differentiation ◽

Signalling Pathway ◽

Skeletal Muscle Differentiation ◽

In Vivo Analysis ◽

Hippocampus Abdominalis

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Trophic Influences of Neurogenic Substances on Skeletal Muscle Differentiation and Growth in Vitro

Nerve-Muscle Cell Trophic Communication ◽

10.1201/9780429282430-6 ◽

2020 ◽

pp. 81-100

Author(s):

Tae H. Oh ◽

George J. Markelonis ◽

Sang H. Shim

Keyword(s):

Skeletal Muscle ◽

Muscle Differentiation ◽

Skeletal Muscle Differentiation

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Cadherins Promote Skeletal Muscle Differentiation in Three-dimensional Cultures

The Journal of Cell Biology ◽

10.1083/jcb.138.6.1323 ◽

1997 ◽

Vol 138 (6) ◽

pp. 1323-1331 ◽

Cited By ~ 84

Author(s):

Ann Redfield ◽

Marvin T. Nieman ◽

Karen A. Knudsen

Keyword(s):

Skeletal Muscle ◽

Cell Adhesion ◽

Three Dimensional ◽

Muscle Differentiation ◽

Skeletal Muscle Differentiation ◽

Skeletal Myogenesis ◽

Bhk Cells ◽

Vitro Model ◽

Cell Cell

The cell–cell adhesion molecule N-cadherin, with its associated catenins, is expressed by differentiating skeletal muscle and its precursors. Although N-cadherin's role in later events of skeletal myogenesis such as adhesion during myoblast fusion is well established, less is known about its role in earlier events such as commitment and differentiation. Using an in vitro model system, we have determined that N-cadherin– mediated adhesion enhances skeletal muscle differentiation in three-dimensional cell aggregates. We transfected the cadherin-negative BHK fibroblastlike cell line with N-cadherin. Expression of exogenous N-cadherin upregulated endogenous β-catenin and induced strong cell–cell adhesion. When BHK cells were cultured as three-dimensional aggregates, N-cadherin enhanced withdrawal from the cell cycle and stimulated differentiation into skeletal muscle as measured by increased expression of sarcomeric myosin and the 12/101 antigen. In contrast, N-cadherin did not stimulate differentiation of BHK cells in monolayer cultures. The effect of N-cadherin was not unique since E-cadherin also increased the level of sarcomeric myosin in BHK aggregates. However, a nonfunctional mutant N-cadherin that increased the level of β-catenin failed to promote skeletal muscle differentiation suggesting an adhesion-competent cadherin is required. Our results suggest that cadherin-mediated cell–cell interactions during embryogenesis can dramatically influence skeletal myogenesis.

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MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

10.21203/rs.3.rs-976465/v1 ◽

2021 ◽

Author(s):

Paromita Dey ◽

Miles A Soyer ◽

Bijan K Dey

Keyword(s):

Skeletal Muscle ◽

Tibialis Anterior Muscle ◽

High Mobility ◽

Muscle Differentiation ◽

Skeletal Muscle Regeneration ◽

Myoblast Differentiation ◽

Skeletal Muscle Differentiation ◽

Muscle Stem Cells ◽

Downstream Target

Abstract Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .

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