Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling

Pansters, N.A.M.; Langen, Ramon; Wouters, Emiel F.M.; Schols, A.M.W.J.

doi:10.1152/japplphysiol.00503.2012

Cited by 19 publications

(19 citation statements)

References 57 publications

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“…This hyperplasic response, along with the apparent increases in fusion efficiency at 48hrs in DEX and MIA compared to CON, would suggest that both treatment conditions have the ability to stimulate and potentially augment myogenesis, albeit in a delayed capacity. An increased differentiation and hypertrophic capacity of C2C12's treated with DEX when co-incubated with IGF-I, has previously been reported [19]. This is thought to occur through the IGF-I-meditated translation of accumulated muscle-specific mRNA transcripts induced by DEX [19] and may in part explain the delayed, yet augmented hyperplasic phenotype observed in the DEX condition presented here.…”

Section: Discussionsupporting

confidence: 66%

“…An increased differentiation and hypertrophic capacity of C2C12's treated with DEX when co-incubated with IGF-I, has previously been reported [19]. This is thought to occur through the IGF-I-meditated translation of accumulated muscle-specific mRNA transcripts induced by DEX [19] and may in part explain the delayed, yet augmented hyperplasic phenotype observed in the DEX condition presented here.…”

Section: Discussionsupporting

confidence: 66%

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

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et al. 2019

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Objective: Osteoarthritis (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. Methods: C2C12 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. Results: Significant 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). Conclusions: These 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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Section: Discussionsupporting

confidence: 66%

Section: Discussionsupporting

confidence: 66%

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

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et al. 2019

Preprint

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“…We found that IGF-1 mildly increased the size of hPSC-CMs, but more importantly proved an essential factor in revealing a positive functional role for the glucocorticoid dexamethasone in this system. Synergistic effects for IGF-1 and dexamethasone have been reported in skeletal muscle and heart, with pro-differentiation and anti-atrophic effects observed ( Chrysis et al., 2011 , Pansters et al., 2013 , Schakman et al., 2008 ). Glucocorticoids also promote the structural and functional maturation of fetal mouse cardiomyocytes ( Rog-Zielinska et al., 2013 , Rog-Zielinska et al., 2015 ) but have little effect on hPSC-CMs when added alone although do affect calcium handling (G.K., C.L.M., M. Bellin, B. van Meer, L. Tertoolen, and S. Casini, unpublished data).…”

Section: Discussionmentioning

confidence: 93%

Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

et al. 2015

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SummaryMaximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

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“…In the present study, we made use of the C 2 C 12 cell culture model to investigate whether GSK-3 inhibition could prevent impaired myogenesis in response to TNF-α and the synthetic GC Dex. Impaired myogenic differentiation in response to TNF-α [80] has been reported previously, and several lines of evidence, including our own work, have demonstrated that, besides their well-described role as inducers of muscle proteolysis, GCs can also cause muscle atrophy by inhibiting several aspects of myogenesis [54,81,82]. …”

Section: Discussionmentioning

confidence: 70%

“…Repeated intranasal LPS instillation in guinea pigs resulted in an increase in plasma cortisol levels (229%, ± 48.4%), which was unaffected by SB213763-treatment (172%, ±SEM 51.2%). Previously it was demonstrated that the synthetic GCs prednisolone as well as Dex strongly impair myogenesis [54]. The addition of Dex to the culture medium during differentiation resulted in impaired C 2 C 12 myotube formation (Figure 4A).…”

Section: Resultsmentioning

confidence: 85%

Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy

et al. 2013

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BackgroundChronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation-associated muscle atrophy.MethodsGuinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor α (TNF-α) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors.ResultsRepeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-α or synthetic GCs was prevented by GSK-3 inhibitors.ConclusionsIn a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD.

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Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling

Abstract: Pansters NA, Langen RC, Wouters EF, Schols AM. Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling.

Cited by 19 publications

References 57 publications

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

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

Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy

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