1. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy;
2. Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems - Eldor Lab, Innovation Accelerator, CNR, Via Piero Gobetti 101, 40129 Bologna, Italy;
3. General Surgery Unit 2 “Clinica Chirurgica” Medical, Surgical and Experimental Sciences Department, University of Sassari, Viale San Pietro 8, 07100, Sassari, Italy;
4. Department of Experimental, Diagnostic and Speciality Medicine (DIMES), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;
5. Azienda Ospedaliero-Universitaria di Sassari, Viale San Pietro 8, 07100, Sassari, Italy;
6. Center for Developmental Biology and Reprogramming- CEDEBIOR, Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100, Sassari, Italy;
7. Institute of Genetic and Biomedic Research, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
*These authors contributed equally to this work
Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2.
Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype.
Keywords: melatonin, epigenetic, gene expression, nutraceuticals, cell differentiation, stem cell fate