caa a22 4500 605521395 CHVBK 20210128100740.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00223-015-9961-0 doi (NATIONALLICENCE)springer-10.1007/s00223-015-9961-0 Glutathione, N -acetylcysteine and Lipoic Acid Down-Regulate Starvation-Induced Apoptosis, RANKL/OPG Ratio and Sclerostin in Osteocytes: Involvement of JNK and ERK1/2 Signalling [Elektronische Daten] [Filippo Fontani, Gemma Marcucci, Teresa Iantomasi, Maria Brandi, Maria Vincenzini] Osteocyte apoptosis due to microdamage and/or oxidative stress is related to increased local bone turnover and resorption observed in various bone diseases. Previous data on osteoblasts and osteoclasts have linked reactive oxygen species and antioxidants to bone remodelling. This study performs a comprehensive analysis on the effect of antioxidants such as glutathione (GSH), N-acetylcysteine and lipoic acid (LA) on starvation-induced osteocyte apoptosis and on cytokines involved in bone remodelling such as the receptor activator kB ligand (RANKL), osteoprotegerin (OPG) and sclerostin. For this study, apoptosis was induced by serum starvation in a murine osteocyte-like cell line MLO-Y4; this condition mimics in part osteocyte apoptosis due to microdamage. The results show that starvation-induced apoptosis and expression of RANKL, OPG and sclerostin are redox regulated processes. All antioxidants are able to inhibit the apoptosis due to starvation. They down-regulate the expression and the release of RANKL, the expression of sclerostin and RANKL/OPG ratio, whereas they only in part up-regulate OPG expression. Antioxidants mediate their effect on starvation-induced apoptosis by JNK signalling and on cytokine expression by both JNK and ERK1/2 activities. This study shows the possible involvement of biological antioxidants such as GSH and LA on redox regulated mechanisms related to apoptosis and expression of cytokines involved in bone remodelling. Moreover, it suggests that both JNK and ERK1/2 may be useful biological targets for drugs affecting bone diseases associated with increased oxidative stress. Springer Science+Business Media New York, 2015 Osteocytes nationallicence Antioxidants nationallicence Apoptosis nationallicence Bone remodelling nationallicence Fontani Filippo Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut Marcucci Gemma Department of Surgery and Translational Medicine, Bone Metabolic Diseases Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy aut Iantomasi Teresa Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut Brandi Maria Department of Surgery and Translational Medicine, Bone Metabolic Diseases Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy aut Vincenzini Maria Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 335-346 0171-967X 96:4<335 2015 96 223 https://doi.org/10.1007/s00223-015-9961-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-9961-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fontani Filippo Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Marcucci Gemma Department of Surgery and Translational Medicine, Bone Metabolic Diseases Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy aut NATIONALLICENCE 700 1- Iantomasi Teresa Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 700 1- Brandi Maria Department of Surgery and Translational Medicine, Bone Metabolic Diseases Unit, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy aut NATIONALLICENCE 700 1- Vincenzini Maria Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 335-346 0171-967X 96:4<335 2015 96 223