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Modulators of Fam210a and Roles of Fam210a in the Function of Myoblasts

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Abstract

Fam210a is a novel protein regulating muscle mass and strength in mice in vivo. However, detailed effects of Fam210a on the function of myoblasts as well as modulators of Fam210a are still unknown. We, thus, investigated (1) the roles of Fam210a in myoblast differentiation, proliferation, apoptosis and degradation, and (2) the factors that regulate Fam210a expression in murine C2C12 cells. We found that the level of Fam210a mRNA was reduced during myoblast differentiation. Reduction in endogenous Fam210a levels by siRNA suppressed mRNA levels of myogenic factors (Pax7, Myf5, Myogenin, and Mhc) and a muscle degradation factor (Murf1). On the other hand, Fam210a siRNA did not affect mRNA encoding the apoptotic factors Bcl-2 and Bax and the extent of apoptosis as measured by ELISA in C2C12 cells. In contrast, Fam210a siRNA increased the mRNA level of Mmp-12, which induces osteoclastogenesis. Interestingly, insulin and 1,25(OH)2D, which are known to affect cell metabolism and muscle function, significantly increased the level of Fam210a mRNA in a dose-dependent manner. In addition, a PI3-kinase inhibitor and reduction in endogenous levels of the vitamin D receptor (VDR) by siRNA suppressed insulin- and 1,25(OH)2D-induced expression of Fam210a, respectively. In conclusion, Fam210a might enhance myoblast differentiation and proteolysis. Moreover, insulin and 1,25(OH)2D may induce myoblast differentiation and degradation by enhancing the expression of Fam210a.

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Abbreviations

Mmp:

Metalloproteinase

Pax:

Paired box protein

Myf:

Myogenic factor

Mhc:

Myosin heavy chain

Murf:

Muscle RING finger

Bcl:

B-cell lymphoma

Bax:

Bcl-2-associated X protein

1,25(OH)2D:

1,25-Dihydroxy vitamin D3

VDR:

Vitamin D receptor

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research (Early-Career Scientists: 18K16202), Academic research support from MSD Life Science Foundation.

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Authors and Affiliations

  1. Department of Internal Medicine 1, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan

    Ken-ichiro Tanaka, Ippei Kanazawa & Toshitsugu Sugimoto

  2. Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montreal, H3T 1E2, Canada

    J. Brent Richards

  3. Calcium Research Laboratory, Metabolic Disorders and Complications Program, Research Institute of the McGill University Health Centre, Montreal, H3T 1E2, Canada

    David Goltzman

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  1. Ken-ichiro Tanaka
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  2. Ippei Kanazawa
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Correspondence to Ippei Kanazawa.

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Ken-ichiro Tanaka, Ippei Kanazawa, J. Brent Richards, David Goltzman and Toshitsugu Sugimoto confirms that they have no conflict of interest.

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Tanaka, Ki., Kanazawa, I., Richards, J.B. et al. Modulators of Fam210a and Roles of Fam210a in the Function of Myoblasts. Calcif Tissue Int 106, 533–540 (2020). https://doi.org/10.1007/s00223-020-00661-y

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  • DOI: https://doi.org/10.1007/s00223-020-00661-y

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