Androgen regulation of satellite cell function

Chen, Yue; Zajac, Jeffrey D; MacLean, Helen E.

doi:10.1677/joe.1.05976

Cited by 114 publications

(101 citation statements)

References 102 publications

(101 reference statements)

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“…The important observations are as follows: a) mRNA expression of the AR is detectable in C2C12 cells and b) AR expression is stimulated by DHT. The expression of AR in the C2C12 cells has also been reported in several other publications (Lee 2002, Chen et al 2005. Although reports about the regulation of AR expression in C2C12 cells are rare, the finding that AR mRNA expression is stimulated by DHT treatment in C2C12 cells is in agreement with the observations made in other cell lines, such as LnCap and PC3 cells (Dai et al 1996).…”

Section: Discussionsupporting

confidence: 83%

“…Muscle cells function as a syncitium, with several nucleated cells fusing to form the muscle fiberthe key cellular activator of this process is the satellite cell . Satellite cells are located beneath the basal lamina of muscle fibers and are a distinct muscle cell subtype responsible for postnatal adaptation, growth, and repair (Mauro 1961, Chen et al 2005. Satellite cells have a variety of potential fates, including proliferation, fusion, and trans-differentiation (Zammit et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

Diel¹,

Baadners²,

Schlüpmann³

et al. 2008

Journal of Molecular Endocrinology

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Androgens are modulators of skeletal muscle adaptation and regeneration processes. The control of satellite cell activity is a key mechanism during this process. In this study, we analyzed the ability of dihydrotestosterone (DHT) and anabolic steroids to induce and modulate the differentiation of C2C12 myoblastoma cells toward myotubes. C2C12 cells were dose-dependently treated with DHT and anabolic steroids. The time-dependent effects on differentiation were measured and correlated with the expression of genes involved in the regulation of satellite cell activity. The distribution of C2C12 cells within the cell cycle was measured by flow cytometry and differentiation by creatine kinase (CK) activity. Gene expression was analyzed using quantitative real-time PCR and confocal microscopy. The treatment with DHT and anabolic steroids resulted in a stimulation of C2C12 cell proliferation and CK activity. The antiandrogen flutamide was able to antagonize this effect. The expression of the androgen receptor, SOX8, SOX9, Delta, Notch, myostatin, and paired box gene7 (Pax7) was modulated by androgens. The treatment with DHT and anabolic steroids resulted in a strong stimulation of myostatin expression not only in undifferentiated cells but also in myotubes. The stimulation could be antagonized by flutamide. The expression of Pax7 was detectable in C2C12 cells early after treatment with DHT. Our results demonstrate that the key mechanisms of satellite cell differentiation are modulated by androgens. Androgens stimulate the proliferation of C2C12 cells, accelerate the process of differentiation, and increase the expression of myostatin in undifferentiated and differentiated cells. Our findings may have implications not only for the treatment of muscular diseases but also for the improvement of doping analytical methods.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

Diel¹,

Baadners²,

Schlüpmann³

et al. 2008

Journal of Molecular Endocrinology

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“…At the cellular level, the effects of testosterone on body composition might involve recruitment or activation of resident myogenic precursor cells to existing myofibers (Chen et al 2005b). Satellite cells cultured from porcine muscle express AR, and AR agonists delay their differentiation (Doumit et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of β-catenin

Gentile¹,

Nantermet²,

Vogel³

et al. 2009

Journal of Molecular Endocrinology

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Androgens promote anabolism in the musculoskeletal system while generally repressing adiposity, leading to lean body composition. Circulating androgens decline with age, contributing to frailty, osteoporosis, and obesity; however, the mechanisms by which androgens modulate body composition are largely unknown. Here, we demonstrate that aged castrated rats develop increased fat mass, reduced muscle mass and strength, and lower bone mass. Treatment with testosterone or 5a-dihydrotestosterone (DHT) reverses the effects on muscle and adipose tissues while only aromatizable testosterone increased bone mass. During the first week, DHT transiently increased soleus muscle nuclear density and induced expression of IGF1 and its splice variant mechano growth factor (MGF) without early regulation of the myogenic factors MyoD, myogenin, monocyte nuclear factor, or myostatin. A genome-wide microarray screen was also performed to identify potential pro-myogenic genes that respond to androgen receptor activation in vivo within 24 h. Of 24 000 genes examined, 70 candidate genes were identified whose functions suggest initiation of remodeling and regeneration, including the type II muscle genes for myosin heavy chain type II and parvalbumin and the chemokine monocyte chemoattractant protein-1. Interestingly, Axin and Axin2, negative regulators of b-catenin, were repressed, indicating modulation of the b-catenin pathway. DHT increased total levels of b-catenin protein, which accumulated in nuclei in vivo. Likewise, treatment of C2C12 myoblasts with both IGF1Ea and MGF C-terminal peptide increased nuclear b-catenin in vitro. Thus, we propose that androgenic anabolism involves early downregulation of Axin and induction of IGF1, leading to nuclear accumulation of b-catenin, a pro-myogenic, anti-adipogenic stem cell regulatory factor.

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“…There are substances that have an anabolic effect on muscle and could potentially counteract the formation of interfiber gaps induced by atrophy, which are known to be filled with fat. Several pharmacological substances influence the development, growth, and repair mechanisms of muscle, namely, anabolic steroids [11][12][13][14][15][16][17][18][19][20] , growth hormones [21][22][23][24] , b-2 agonists, heparan sulfate 25 , xanthine derivatives 26 , creatine 27 , and vitamin D 28 . Of all of these substances, anabolic steroids seem best suited for clinical application.…”

mentioning

confidence: 99%

Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits

Gerber

Meyer

Nuss

et al. 2011

Journal of Bone and Joint Surgery

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To our knowledge, this is the first documentation of partial prevention of important muscle alterations after retraction of the supraspinatus musculotendinous unit caused by tendon disruption. Nandrolone decanoate administration in the phase after tendon release prevented fatty infiltration of the supraspinatus muscle and reduced functional muscle impairment caused by myotendinous retraction in this rabbit rotator cuff model, but two of seven rabbits that received the drug developed infections. Background: Muscles of the rotator cuff undergo retraction, atrophy, and fatty infiltration after a chronic tear, and a rabbit

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Androgen regulation of satellite cell function

Cited by 114 publications

References 102 publications

C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression

Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of β-catenin

Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits

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