The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis |
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| Institution: | 1. University Hospital, Division of Cranio-Maxillofacial and Oral Surgery and University of Zurich, Center of Dental Medicine, Oral Biotechnology & Bioengineering, Plattenstrasse 11, 8032 Zürich, Switzerland;3. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland;4. CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland;1. Department of Prosthodontics Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, PR China;2. Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong 510055, PR China;3. Shanghai Tenth People''s Hospital, Tongji University School of Medicine, Shanghai 200072, PR China;4. Guangdong No. 2 Provincial People''s Hospital, Guangzhou, Guangdong 510317, PR China;5. Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, Guangdong 510800, PR China;6. Huizhou Stomatological Hospital Zhong Kai Branch, Huizhou, Guangdong 516006, PR China;1. Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506-9196, USA;2. Division of Exercise Physiology, West Virginia University, Morgantown, WV 26506-9227, USA;3. Department of Biostatistics, West Virginia University, Morgantown, 26506-9190, USA;1. The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, PR China;2. Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, PR China;1. Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China;2. Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, China;1. Department of Epidemiological Methods and Etiologic Research, Leibniz Institute for Prevention Research and Epidemiology — BIPS, Achterstr. 30, 28359 Bremen, Germany;2. Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology — BIPS, Achterstr. 30, 28359 Bremen, Germany;3. Research Centre in Epidemiology and Preventive Medicine — EPIMED, Department of Clinical and Experimental Medicine, University of Insubria, Via O Rossi 9, 21100 Varese, Italy;4. Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Via dell''Elettronica, 86077 Pozzilli, Italy;5. Department of Chronic Diseases, Centre of Behavioural and Health Sciences, National Institute for Health Development, Hiiu St 42, 11619 Tallinn, Estonia;6. Department of Public Health and Community Medicine, University of Gothenburg, Medicinaregatan 16, 40530 Gothenburg, Sweden;7. Department of Paediatrics, Queen Silvia Children''s Hospital, University of Gothenburg, Rondvägen 10, SE 41686 Gothenburg, Sweden;8. Department of Pediatrics, University of Pécs, József A. u. 7, 7623 Pécs, Hungary;9. GENUD (Growth, Exercise, Nutrition and Development) Research Group, University School of Health Sciences, University of Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain;10. Institute of Food Sciences, National Research Council, Via Roma 64, 83100 Avellino, Italy;11. Department of Public Health, Ghent University, UZ 2 Blok A De Pintelaan 185, 9000 Ghent, Belgium;12. Faculty of Mathematics and Computer Science, Bremen University, Bibliothekstr. 1, 28359 Bremen, Germany;1. Northeast Ohio Medical University, Akron, OH, USA;2. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MD, USA;3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;4. Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;5. Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;6. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA |
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| Abstract: | Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption.In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized (OVX) induced rats while treated systemically with NMP. Female Sprague–Dawley rats were ovariectomized and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed. 15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average by 43% and improved bone mineral density (BMD) and bone volume over total volume (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group.Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis. |
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