Expression of β-catenin is necessary for physiological growth of adult skeletal muscle

2006 ◽  
Vol 291 (1) ◽  
pp. C185-C188 ◽  
Author(s):  
Dustin D. Armstrong ◽  
Vicki L. Wong ◽  
Karyn A. Esser

Expression of β-catenin is known to be important for developmental processes such as embryonic pattern formation and determination of cell fate. Inappropriate expression, however, has been linked to pathological states such as cancer. Here we report that expression of β-catenin is necessary for physiological growth of skeletal muscle in response to mechanical overload. Conditional inactivation of β-catenin was induced in control and overloaded muscle through intramuscular injection of adenovirus expressing Cre recombinase in β-catenin floxed mice. Individual muscle fiber analysis was performed to identify positively transfected/inactivated cells and determine fiber cross-sectional area. The results demonstrate that fiber growth is completely inhibited when the β-catenin expression is lost. This effect was cell autonomous, as fibers that did not exhibit recombination in the floxed mice grew to the same magnitude as infected/noninfected fibers from wild-type mice. These findings suggest that β-catenin may be a primary molecular site through which multiple signaling pathways converge in regulating physiological growth.

Development ◽  
2012 ◽  
Vol 139 (12) ◽  
pp. e1208-e1208
Author(s):  
B. Gayraud-Morel ◽  
F. Chretien ◽  
A. Jory ◽  
R. Sambasivan ◽  
E. Negroni ◽  
...  

2010 ◽  
Vol 108 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Satyanarayana Paturi ◽  
Anil K. Gutta ◽  
Sunil K. Kakarla ◽  
Anjaiah Katta ◽  
Eric C. Arnold ◽  
...  

The effect of insulin resistance (IR) on the adaptation of skeletal muscle loading is not well understood. Here we examine whether the soleus muscles of the lean Zucker (LZ) and insulin-resistant obese Zucker (OZ) rat exhibit differences in their ability to undergo muscle hypertrophy following 8 wk of mechanical overload. Four-week-old male LZ ( n = 5) and OZ ( n = 5) rats underwent unilateral surgical ablation of the gastrocnemius muscle while the contralateral hindlimb was used as an internal control. Mechanical overload increased soleus muscle wet weight (LZ 57% and OZ 33%, respectively; P < 0 .05) and average type 1 fiber cross-sectional area (LZ 32% and OZ 5%, respectively; P < 0.05) in LZ and OZ rats, while the magnitude of these increases was greater in the LZ animals ( P < 0 .05). The reduced degree of muscle hypertrophy observed in the OZ animals was associated with decreases in the ability of the OZ soleus muscle to phosphorylate p70s6kThr 389 and mTOR, while phosphorylation of p70s6kThr 389 was increased in the LZ overloaded soleus by 83% ( P < 0 .05). The amount of Tuberin/TSC2 phosphorylation, an inhibitor of mTOR, was unchanged in the LZ soleus after overload while it was increased (68.3%, P < 0.05) in OZ animals. Conversely, AMPK phosphorylation was decreased in the LZ (−22.77%, P < 0 .05) but increased (57%, P < 0 .05) in the OZ soleus with overload. Taken together, these data suggest that IR or other related comorbidities may impair the ability of the soleus to activate mTOR signaling and undergo load-induced muscle hypertrophy.


2012 ◽  
Vol 125 (24) ◽  
pp. 6198-6198 ◽  
Author(s):  
B. Gayraud-Morel ◽  
F. Chretien ◽  
A. Jory ◽  
R. Sambasivan ◽  
E. Negroni ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Minas Nalbandian ◽  
Zsolt Radak ◽  
Masaki Takeda

Lactate is one of the metabolic products of glycolysis. It is widely accepted as an important energy source for many cell types and more recently has been proposed to actively participate in cell-cell communication. Satellite cells (SCs), which are adult skeletal muscle stem cells, are the main players of the skeletal muscle regeneration process. Recent studies have proposed a metabolic switch to increase glycolysis in activated SCs. Moreover, lactate has been shown to affect SCs and myoblasts in vivo and in vitro. In this short review, we describe how metabolic variations relate with SC fate (quiescence, activation, proliferation, migration, differentiation, fusion, and self-renewal), as well as discuss possible relationships between lactate as a metabolite and as a signaling molecule affecting SC fate.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thibaut Desgeorges ◽  
Sophie Liot ◽  
Solene Lyon ◽  
Jessica Bouvière ◽  
Alix Kemmel ◽  
...  

2012 ◽  
Vol 125 (7) ◽  
pp. 1738-1749 ◽  
Author(s):  
B. Gayraud-Morel ◽  
F. Chretien ◽  
A. Jory ◽  
R. Sambasivan ◽  
E. Negroni ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1171
Author(s):  
Simone Vumbaca ◽  
Giulio Giuliani ◽  
Valeria Fiorentini ◽  
Flavia Tortolici ◽  
Andrea Cerquone Perpetuini ◽  
...  

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell–cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell–cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1α and IL1β potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche.


2020 ◽  
Author(s):  
Assia Derfoul ◽  
Iago Pinal-Fernandez ◽  
Wilson Huang ◽  
Cassie Parks ◽  
Katherine Pak ◽  
...  

Abstract The chromodomain helicase and DNA binding 4 (CHD4) protein is upregulated in regenerating myofibers. To define the role of CHD4 in muscle differentiation and regeneration, we generated mice with CHD4 ablated in muscle satellite cells (SCs). Embryonic day 18.5 CHD4 KO mice are non-viable, with atrophic intercostal and back muscles and altered expression of muscle contraction genes. Tamoxifen-inducible conditional CHD4 KO in adult mouse SCs diminished myoblast proliferation, induced premature differentiation, and altered expression of muscle contraction genes at the myotube stage. Following cardiotoxin–induced muscle injury, CHD4 KO regenerating myofibers had reduced cross-sectional area. ChIP-Seq analysis revealed that CHD4 binds actin a1, Wnt and b-catenin genes, which are known to play roles in the regulation of myogenesis. Together, our results suggest an important role for CHD4 in the control of embryonic myogenesis, SC differentiation, and the control of muscle fiber size in adult skeletal muscle during regeneration.


2021 ◽  
Author(s):  
Rita De Gasperi ◽  
Chenglin Mo ◽  
Daniella Azulai ◽  
Zhiying Wang ◽  
Lauren M Harlow ◽  
...  

Background: The role of Numb, a protein that is important for cell fate and development was investigated in adult skeletal muscle in mice using a conditional, inducible knockout (cKO) model. Methods: Numb expression was evaluated by Western blot. Numb localization was determined by confocal microscopy. The effects of cKO of Numb and the closely-related gene Numb-like in skeletal muscle fibers was evaluated by in-situ physiology; transmission and focused ion beam scanning electron microscopy; 3-dimensional reconstruction of mitochondrial; lipidomics; and bulk RNA-sequencing. Additional studies using primary mouse myotubes investigated the effects the effects of Numb knockdown on cell fusion, mitochondrial function and calcium transients. Results: Numb protein expression was reduced by ~70% (p < 0.01) at 24 as compared to 3 months of age. Numb was localized within muscle fibers as bands traversing fibers at regularly spaced intervals in close proximity to dihydropyridine receptors. The cKO of Numb and Numb-like reduced specific tetanic force by 36%, p < 0.01), altered mitochondrial spatial relationships to sarcomeric structures, increased Z-line spacing by 30% (p < 0.0001), perturbed sarcoplasmic reticulum organization and reduced mitochondrial volume by over 80% (p < 0.01). Only six genes were differentially expressed in cKO mice: Itga4, Sema7a, Irgm2, Vezf1, Mib1 and Tmem132a. Several lipid mediators derived from polyunsaturated fatty acid (PUFAs) through lipoxygenases were upregulated in Numb cKO skeletal muscle; 12-HEPE was increased by ~250% (p < 0.05) and 17,18-EpETE by ~240% (p < 0.05). In mouse primary myotubes, Numb knock-down reduced cell fusion (~20%, p < 0.01) and mitochondrial function and delayed the caffeine-induced rise in cytosolic calcium concentrations by more than 100% (p < 0.01). Conclusions: These findings implicate Numb as a critical factor in skeletal muscle structure and function which appear to be critical for calcium release; we therefore speculate Numb plays critical roles in excitation-contraction coupling, one of the putative targets of aged skeletal muscles. These findings provide new insights into the molecular underpinnings of the loss of muscle function observed with sarcopenia.


Author(s):  
T.B. Ball ◽  
W.M. Hess

It has been demonstrated that cross sections of bundles of hair can be effectively studied using image analysis. These studies can help to elucidate morphological differences of hair from one region of the body to another. The purpose of the present investigation was to use image analysis to determine whether morphological differences could be demonstrated between male and female human Caucasian terminal scalp hair.Hair samples were taken from the back of the head from 18 caucasoid males and 13 caucasoid females (Figs. 1-2). Bundles of 50 hairs were processed for cross-sectional examination and then analyzed using Prism Image Analysis software on a Macintosh llci computer. Twenty morphological parameters of size and shape were evaluated for each hair cross-section. The size parameters evaluated were area, convex area, perimeter, convex perimeter, length, breadth, fiber length, width, equivalent diameter, and inscribed radius. The shape parameters considered were formfactor, roundness, convexity, solidity, compactness, aspect ratio, elongation, curl, and fractal dimension.


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