Vitamin D and VDR in cancer cachexia and muscle regeneration
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Andrea Camperi1,5,*, Fabrizio Pin1,2,*, Domiziana Costamagna1,2,8, Fabio Penna1,2, Maria Lopez Menduina1,3, Zaira Aversa4, Teresa Zimmers5, Roberto Verzaro6, Raffaella Fittipaldi7, Giuseppina Caretti7, Francesco Maria Baccino1, Maurizio Muscaritoli4, Paola Costelli1,2
1Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
2Interuniversity Institute of Myology, Italy
3Department of Physiology, Complutense University of Madrid, Madrid, Spain
4Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
5Indiana University School of Medicine - IUPUI, Indianapolis, IN, USA
6Department of Surgery, M.G. Vannini Hospital, Rome, Italy
7Department of Biosciences, University of Milan, Milan, Italy
8Current address: Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology, Department of Development and Regeneration, University Hospital Gasthuisberg, Leuven, Belgium
*Andrea Camperi and Fabrizio Pin equally contributed to the present study
Paola Costelli, email: [email protected]
Keywords: muscle wasting, regeneration, vitamin D receptor, myogenin, circulating vitamin D
Received: July 28, 2016 Accepted: January 27, 2017 Published: February 21, 2017
Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumor-bearing animals.
Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass.
The effects of vitamin D on muscle cells were studied in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly, fusing only partially and forming multinucleated structures with aberrant shape and low myosin heavy chain content. Vitamin D treatment resulted in VDR overexpression and myogenin down-regulation. Silencing VDR expression in C2C12 cultures abrogated the inhibition of differentiation exerted by vitamin D treatment.
These data suggest that VDR overexpression in tumor-bearing animals contributes to muscle wasting by impairing muscle regenerative program. In this regard, attention should be paid when considering vitamin D supplementation to patients affected by chronic pathologies where muscle regeneration may be involved.
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