Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation<i>in vitro</i>by suppressing Sox-9 expression

Elkasrawy, Moataz N.; Fulzele, Sadanand; Bowser, Matthew; Wenger, Karl; Hamrick, Mark W.

doi:10.3109/08977194.2011.599324

Cited by 32 publications

(29 citation statements)

References 45 publications

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“…In addition, the proliferation rate of chondrocytes isolated from the epiphyseal growth plates of mstn Ϫ/Ϫ mice is greater than that of cells from WT mice (79). Notwithstanding, our study failed to detect significant differences in the number of bone LRCs in WT and mstn Ϫ/Ϫ mice, regardless of region.…”

Section: Discussioncontrasting

confidence: 74%

Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Jackson

Rodgers

2014

Endocrinology

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Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn(-/-) (Jekyll) backgrounds in which slow-cycling stem, transit-amplifying, and progenitor cells are preferentially labeled by histone 2B/green fluorescent protein. Jekyll mice were born with fewer label-retaining cells (LRCs) in muscle and heart, consistent with increased stem/progenitor cell contributions to embryonic growth of both tissues. Cardiac LRC recruitment from noncardiac sources occurred in both groups, but lasted longer in Jekyll hearts, whereas heightened β-adrenergic sensitivity of mstn(-/-) hearts was explained by elevated SERCA2a, phospholamban, and β2-adrenergic receptor levels. Jekyll mice were also born with more adipose LRCs despite significantly smaller tissue weights. Reduced adiposity in mstn(-/-) animals is therefore due to reduced lipid deposition as adipoprogenitor pools appear to be enhanced. By contrast, increased bone densities of mstn(-/-) mice are likely compensatory to hypermuscularity because LRC counts were similar in Jekyll and wild-type tibia. Myostatin therefore significantly influences the potency of different tissues, not just muscle, as well as cardiac Ca²⁺-handling proteins. Thus, the pleiotropic phenotype of mstn(-/-) animals may not be due to enhanced muscle development per se, but also to altered stem/progenitor cell pools that ultimately influence tissue potency.

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Section: Discussioncontrasting

confidence: 74%

Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Jackson

Rodgers

2014

Endocrinology

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“…However, bone marrow-derived MSCs obtained from myostatinnull mice exhibited increased osteogenic differentiation compared with cells from wild-type mice (13), and myostatin expression increased transiently after fracture (47). Myostatin treatment reduced type II collagen synthesis and expression of Sox9 mRNA, a transcription factor for chondrocyte differentiation (48). Thus, it is tempting to speculate that myostatin may promote the differentiation of MSC or MSC-derived cells into osteoblastic cells, an important step in the initiation of AAC.…”

Section: Discussionmentioning

confidence: 97%

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Szulc¹,

Hofbauer²,

Rauner³

et al. 2012

European Journal of Endocrinology

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Objective: To assess the association between abdominal aortic calcification (AAC) and serum levels of myostatin, a negative regulator of skeletal muscle mass, which has been implicated in the development of atherosclerotic lesions in mice. Design and patients: We assessed AAC semiquantitatively from the lateral spine scans obtained using dual energy X-ray absorptiometry in 1071 men aged 20-87 years. Serum myostatin levels were measured by an immunoassay that detects all myostatin forms. Results: Total myostatin serum levels did not differ between men with or without self-reported ischemic heart disease, hypertension, or diabetes mellitus. Total serum myostatin levels were higher in men with higher serum calcium levels and lower in men with higher serum concentrations of highly sensitive C-reactive protein. Men with AAC had lower myostatin levels compared with men without AAC. Prevalence of AAC (AAC score O0) was lower in the highest myostatin quartile compared with the three lower quartiles (P!0.05). After adjustment for confounders, odds of AAC (AAC score O0) were lower (ORZ0.62; 95% confidence interval (95% CI), 0.45-0.85; P!0.005) for the fourth myostatin quartile vs the three lower quartiles combined. In the sub-analysis of 745 men aged R60 years, the results were similar: AAC prevalence was lower in the highest myostatin quartile compared with the three lower quartiles combined (ORZ0.54; 95% CI, 0.38-0.78; P!0.001). Conclusions: In older men, total myostatin serum levels are inversely correlated with AAC. Further studies are needed to investigate mechanisms underlying this association and to assess utility of myostatin as a cardiovascular marker.

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“…Previous work in our lab showed that myostatin can inhibit the proliferation of aged bone marrow stromal cells (Bowser et al, 2013), that bone marrow stromal cells from mice lacking myostatin show increased proliferation (Elkasrawy et al, 2011), and that myostatin can inhibit chondrogenesis in vivo and in vitro (Elksrawy et al, 2012). These data may at least in part explain the increased fracture callus size following osteotomy in mice lacking myostatin (Kellum et al, 2009), and increased fracture callus bone volume in mice treated with myostatin propeptide following osteotomy (Hamrick et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength

Arounleut

Bialek

Liang

et al. 2013

Experimental Gerontology

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Loss of muscle and bone mass with age are significant contributors to falls and fractures among the elderly. Myostatin deficiency is associated with increased muscle mass in mice, dogs, cows, sheep and humans, and mice lacking myostatin have been observed to show increased bone density in the limb, spine, and jaw. Transgenic overexpression of myostatin propeptide, which binds to and inhibits the active myostatin ligand, also increases muscle mass and bone density in mice. We therefore sought to test the hypothesis that in vivo inhibition of myostatin using an injectable myostatin propeptide (GDF8 propeptide-Fc) would increase both muscle mass and bone density in aged (24 mo) mice. Mice were injected weekly (20 mg/kg body weight) with recombinant myostatin propeptide-Fc (PRO) or vehicle (VEH; saline) for four weeks. There was no difference in body weight between the two groups at the end of the treatment period, but PRO treatment significantly increased mass of the tibialis anterior muscle (+7%) and increased muscle fiber diameter of the extensor digitorum longus (+16%) and soleus (+6%) muscles compared to VEH treatment. Bone volume relative to total volume (BV/TV) of the femur calculated by microCT did not differ significantly between PRO- and VEH-treated mice, and ultimate force (Fu), stiffness (S), toughness (U) measured from three-point bending tests also did not differ significantly between groups. Histomorphometric assays also revealed no differences in bone formation or resorption in response to PRO treatment. These data suggest that while developmental perturbation of myostatin signaling through either gene knockout or transgenic inhibition may alter both muscle and bone mass in mice, pharmacological inhibition of myostatin in aged mice has a more pronounced effect on skeletal muscle than on bone.

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Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferationin vitroby suppressing Sox-9 expression

Cited by 32 publications

References 45 publications

Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength

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