Shenoy P., Sudheer, Bose, Bipasha, Sharma, Mridula, McFarlane, Craig, and Kambadur, Ravi (2014) Lack of Myostatin reduces MyoD induced myogenic potential of primary muscle fibroblasts. Journal of Cellular Biochemistry, 115 (11). pp. 1908-1917.

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Abstract

Conversion of skin fibroblasts into myoblasts by transducing the cells with myogenic master regulator MyoD has been in practice for more thantwo decades. The purpose of such conversion is due to scarcity of muscle biopsies during muscle wasting, hence conversion of fibroblasts tomyogenic lineage from various genetic backgrounds offers a great alternative for cell therapies. Here, we have investigated if eliminatingMyostatin, a potent negative regulator of myogenesis, could improve the myogenic conversion of fibroblasts. In the present study, we haveisolated primary muscle fibroblasts from the skeletal muscles of wild-type (WT) and myostatin null (Mstn -/-) mice and transduced the musclefibroblasts with MyoD using adenoviral, lentiviral transduction, and electroporation methods. In contrast to what we predicted, it is only in WTmuscle fibroblasts we detected significant ectopic expression of MyoD, and myogenic conversion. Muscle fibroblasts from Mstn -/- genotypefailed to take up as much MyoD using the three methods and, therefore, failed to form myotubes. The aforesaid condition of greater MyoDuptake by WT muscle fibroblasts was attributed to the presence of adenoviral receptors, which facilitated adenoviral transduction. However, in Mstn -/- fibroblasts we detected negligible levels of adenovirus receptors. Moreover, we also detected significantly higher levels of MyoDantagonists, c-Fos, c-Jun, and cyclin D1 in Mstn -/- muscle fibroblasts. Taken together, our results demonstrate that lack of myostatin reducesmyogenic potential of muscle fibroblasts by inhibiting MyoD function.

Item ID:	52342
Item Type:	Article (Research - C1)
ISSN:	1097-4644
Funders:	Nanyang Technological University, Singapore, National Research Foundation (NRF) Singapore
Projects and Grants:	NRF 138602
Date Deposited:	13 Feb 2018 03:49
FoR Codes:	06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 30% 10 TECHNOLOGY > 1004 Medical Biotechnology > 100404 Regenerative Medicine (incl Stem Cells and Tissue Engineering) @ 40% 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 30%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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