Camperi, AndreaPin, FabrizioCostamagna, DomizianaPenna, FabioLopez Menduina, MariaAversa, ZairaZimmers, Teresa A.Verzaro, RobertoFittipaldi, RaffaellaCaretti, GiuseppinaBaccino, Francesco MariaMuscaritoli, MaurizioCostelli, Paola2018-03-142018-03-142017-03-28Camperi, A., Pin, F., Costamagna, D., Penna, F., Menduina, M. L., Aversa, Z., … Costelli, P. (2017). Vitamin D and VDR in cancer cachexia and muscle regeneration. Oncotarget, 8(13), 21778–21793. http://doi.org/10.18632/oncotarget.15583https://hdl.handle.net/1805/15514Low 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.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesMuscle wastingRegenerationVitamin D receptorMyogeninCirculating vitamin DArticle