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Effects of 1,25(OH) 2 D 3 and 25(OH)D 3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy
Author(s) -
van der Meijden K.,
Bravenboer N.,
Dirks N.F.,
Heijboer A.C.,
den Heijer M.,
de Wit G.M.J.,
Offringa C.,
Lips P.,
Jaspers R.T.
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25388
Subject(s) - c2c12 , myocyte , muscle hypertrophy , chemistry , microbiology and biotechnology , biology , myogenesis , endocrinology
An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH) 2 D by 1α‐hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH) 2 D 3 and 25(OH)D 3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D 3 and 1,25(OH) 2 D 3 . We show that myoblasts not only responded to 1,25(OH) 2 D 3 , but also to the precursor 25(OH)D 3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH) 2 D 3 as well as 25(OH)D 3 stimulated VDR mRNA expression and in myotubes 1,25(OH) 2 D 3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D 3 metabolism. Although 1α‐hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH) 2 D 3 or 25(OH)D 3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D 3 to 24R,25(OH) 2 D 3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D 3 metabolites, but is also able to metabolize 25(OH)D 3 and 1,25(OH) 2 D 3 . J. Cell. Physiol. 231: 2517–2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.