Plasmonic fusion between fibroblasts and skeletal muscle cells for skeletal muscle regeneration

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.

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Monosodium Iodoacetate delays regeneration and inhibits hypertrophy in skeletal muscle cells in vitro

10.1101/577866 ◽

2019 ◽

Author(s):

Rowan P. Rimington ◽

Darren J. Player ◽

Neil R.W. Martin ◽

Mark P. Lewis

Keyword(s):

Skeletal Muscle ◽

Muscle Cells ◽

Rodent Model ◽

Skeletal Muscle Cells ◽

Skeletal Muscle Regeneration ◽

Index Number ◽

Monosodium Iodoacetate ◽

The Impact

AbstractObjectiveOsteoarthritis (OA) is a musculoskeletal disease which contributes to severe morbidity. The monosodium iodoacetate (MIA) rodent model of OA is now well established, however the effect of MIA on surrounding tissues post injection has not been investigated and as such the impact on phenotypic development is unknown. The aim of this investigation was to examine the impact of MIA incubation on skeletal muscle cells in vitro, to provide an indication as to the potential influence of MIA administration of skeletal muscle in vivo.MethodsC2C12 skeletal muscle myotubes were treated with either 4.8μM MIA or 10μM Dexamethasone (DEX, positive atrophic control) up to 72hrs post differentiation and sampled for morphological and mRNA analyses.ResultsSignificant morphological effects (fusion index, number of myotubes and myotube width, p<0.05) were evident, demonstrating a hypertrophic phenotype in control (CON) compared to a hyperplasic phenotype in MIA and DEX. Increases in MAFbx mRNA were also evident between conditions, with post-hoc analysis demonstrating significance between CON and DEX (p<0.001), but not between CON and MIA (p>0.05).ConclusionsThese data indicate a significant impact of both DEX and MIA on regeneration and hypertrophy in vitro and suggest differential activating mechanisms. Future investigations should determine whether skeletal muscle regeneration and hypertrophy is affected in the in vivo rodent model and the potential impact this has on the OA phenotypic outcome.

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Cytokine Response of Cultured Skeletal Muscle Cells Stimulated with Proinflammatory Factors Depends on Differentiation Stage

The Scientific World JOURNAL ◽

10.1155/2013/617170 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Matej Podbregar ◽

Mitja Lainscak ◽

Oja Prelovsek ◽

Tomaz Mars

Keyword(s):

Skeletal Muscle ◽

Interleukin 1 ◽

Muscle Cells ◽

Cytokine Response ◽

Skeletal Muscle Cells ◽

Skeletal Muscle Regeneration ◽

Inflammatory Factors ◽

Cytokine Signaling ◽

Cell Proliferation And Differentiation ◽

Differentiation Stage

Myoblast proliferation and myotube formation are critical early events in skeletal muscle regeneration. The attending inflammation and cytokine signaling are involved in regulation of skeletal muscle cell proliferation and differentiation. Secretion of muscle-derived cytokines upon exposure to inflammatory factors may depend on the differentiation stage of regenerating muscle cells. Cultured human myoblasts and myotubes were exposed to 24-hour treatment with tumor necrosis factor (TNF)-αor lipopolysaccharide (LPS). Secretion of interleukin 6 (IL-6), a major muscle-derived cytokine, and interleukin 1 (IL-1), an important regulator of inflammatory response, was measured 24 hours after termination of TNF-αor LPS treatment. Myoblasts pretreated with TNF-αor LPS displayed robustly increased IL-6 secretion during the 24-hour period after removal of treatments, while IL-1 secretion remained unaltered. IL-6 secretion was also increased in myotubes, but the response was less pronounced compared with myoblasts. In contrast to myoblasts, IL-1 secretion was markedly stimulated in LPS-pretreated myotubes. We demonstrate that preceding exposure to inflammatory factors stimulates a prolonged upregulation of muscle-derived IL-6 and/or IL-1 in cultured skeletal muscle cells. Our findings also indicate that cytokine response to inflammatory factors in regenerating skeletal muscle partially depends on the differentiation stage of myogenic cells.

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Electroactive, Multi-Component Scaffolds for Skeletal Muscle Regeneration

ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology ◽

10.1115/nemb2013-93197 ◽

2013 ◽

Cited By ~ 1

Author(s):

K. D. McKeon-Fischer ◽

D. H. Flagg ◽

J. H. Rossmeisl ◽

A. R. Whittington ◽

J. W. Freeman

Keyword(s):

Skeletal Muscle ◽

Muscle Cells ◽

Scar Tissue ◽

Quadriceps Muscle ◽

Skeletal Muscle Cells ◽

Skeletal Muscle Regeneration ◽

Skeletal Muscle Function ◽

Functional Movement ◽

Restoration Method

After loss of skeletal muscle function due to traumatic injuries, muscle healing may result in scar tissue formation and reduced function. A restoration method is needed to create a bioartificial muscle that supports cell growth. An electroactive, coaxial electrospun scaffold was created using PCL, MWCNT, and a PAA/PVA hydrogel. This scaffold was conductive and displayed an actuation response when electrically stimulated. Rat primary skeletal muscle cells were biocompatible with the scaffold and displayed multi-nucleated constructs with actin interaction. MWCNT toxicity was tested using a single exposure method on rat primary skeletal muscle cells. A decrease in cellular activity was found on day 14, but a recovering trend was observed on days 21 and 28. Scaffolds were implanted in the quadriceps muscle of rats for in vivo biocompatibility investigation. Muscle cells were found to have attached and infiltrated the PCL-MWCNT-PAA/PVA scaffolds over the 28 day period. Further development of this scaffold would lead to a viable option for a bioartificial muscle as it is biocompatible and may provide some functional movement to the patient.

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