{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:51:35Z","timestamp":1790034695670,"version":"4.0.1"},"reference-count":110,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A 140868"],"award-info":[{"award-number":["31003A 140868"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epigenetics describes mechanisms which control gene expression and cellular processes without changing the DNA sequence. The main mechanisms in epigenetics are DNA methylation in CpG-rich promoters, histone modifications and non-coding RNAs (ncRNAs). DNA methylation modifies the function of the DNA and correlates with gene silencing. Histone modifications including acetylation\/deacetylation and phosphorylation act in diverse biological processes such as transcriptional activation\/inactivation and DNA repair. Non-coding RNAs play a large part in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional level. Osteoporosis is the most common skeletal disorder, characterized by compromised bone strength and bone micro-architectural deterioration that predisposes the bones to an increased risk of fracture. It is most often caused by an increase in bone resorption that is not sufficiently compensated by a corresponding increase in bone formation. Nowadays it is well accepted that osteoporosis is a multifactorial disorder and there are genetic risk factors for osteoporosis and bone fractures. Here we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling.<\/jats:p>","DOI":"10.3390\/ijms17091446","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T10:04:28Z","timestamp":1472724268000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["Epigenetic Regulation of Bone Remodeling and Its Impacts in Osteoporosis"],"prefix":"10.3390","volume":"17","author":[{"given":"Chafik","family":"Ghayor","sequence":"first","affiliation":[{"name":"Oral Biotechnology & Bioengineering, Center for Dental Medicine, Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich 8032, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-2296","authenticated-orcid":false,"given":"Franz","family":"Weber","sequence":"additional","affiliation":[{"name":"Oral Biotechnology & Bioengineering, Center for Dental Medicine, Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich 8032, Switzerland"},{"name":"CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich 8057, Switzerland"},{"name":"Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"ref_1","first-page":"1353","article-title":"Physiology and pathophysiology of bone remodeling","volume":"45","author":"Raisz","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.ecl.2005.07.009","article-title":"Pathophysiology of age-related bone loss and osteoporosis","volume":"34","author":"Khosla","year":"2005","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2217\/epi.11.22","article-title":"Epigenetics and lifestyle","volume":"3","author":"Baccarelli","year":"2011","journal-title":"Epigenomics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/MOP.0b013e32832925cc","article-title":"Epigenetics and environmental chemicals","volume":"21","author":"Baccarelli","year":"2009","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1749-6632.2011.06245.x","article-title":"Epigenetic regulation of osteoclast differentiation","volume":"1240","author":"Yasui","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.4161\/cc.8.6.7938","article-title":"Epigenetic patterns of embryonic and adult stem cells","volume":"8","author":"Yao","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1093\/hmg\/9.16.2395","article-title":"The DNA methyltransferases of mammals","volume":"9","author":"Bestor","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0070-2153(04)60003-2","article-title":"Structure and function of eukaryotic DNA methyltransferases","volume":"60","author":"Chen","year":"2004","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1056\/NEJMra072067","article-title":"Epigenetics in cancer","volume":"358","author":"Esteller","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrc1279","article-title":"The history of cancer epigenetics","volume":"4","author":"Feinberg","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1045","article-title":"The power and the promise of DNA methylation markers","volume":"3","author":"Laird","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/ng1941","article-title":"Epigenetic stem cell signature in cancer","volume":"39","author":"Widschwendter","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/jcb.21291","article-title":"Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation","volume":"102","author":"Kang","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41083","DOI":"10.1074\/jbc.M111.258715","article-title":"GADD45A protein plays an essential role in active DNA demethylation during terminal osteogenic differentiation of adipose-derived mesenchymal stem cells","volume":"286","author":"Zhang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20120","DOI":"10.1074\/jbc.M114.558064","article-title":"Epigenetic modifications and canonical wingless\/int-1 class (WNT) signaling enable trans-differentiation of nonosteogenic cells into osteoblasts","volume":"289","author":"Cho","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4161\/epi.7.1.18753","article-title":"Role of DNA methylation in the regulation of the RANKL-OPG system in human bone","volume":"7","author":"Sanudo","year":"2012","journal-title":"Epigenetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nm.3774","article-title":"DNA methyltransferase 3a regulates osteoclast differentiation by coupling to an S-adenosylmethionine-producing metabolic pathway","volume":"21","author":"Nishikawa","year":"2015","journal-title":"Nat. Med."},{"key":"ref_20","first-page":"698","article-title":"The role of DNA methylation in common skeletal disorders","volume":"1","author":"Riancho","year":"2012","journal-title":"Biology (Basel)"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/jbmr.1491","article-title":"DNA methylation contributes to the regulation of sclerostin expression in human osteocytes","volume":"27","author":"Sanudo","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.bone.2011.06.006","article-title":"Epigenetic regulation of alkaline phosphatase in human cells of the osteoblastic lineage","volume":"49","author":"Sanudo","year":"2011","journal-title":"Bone"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1016\/j.jbiomech.2010.07.033","article-title":"The epigenetic mechanism of mechanically induced osteogenic differentiation","volume":"43","author":"Arnsdorf","year":"2010","journal-title":"J. Biomech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.bbamcr.2011.01.022","article-title":"DNA methylation restricts spontaneous multi-lineage differentiation of mesenchymal progenitor cells, but is stable during growth factor-induced terminal differentiation","volume":"1813","author":"Hupkes","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S1016-8478(23)17408-5","article-title":"Methylation of the mouse DIx5 and Osx gene promoters regulates cell type-specific gene expression","volume":"22","author":"Lee","year":"2006","journal-title":"Mol. Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"252","DOI":"10.2174\/138920212800543129","article-title":"Do epigenetic marks govern bone mass and homeostasis?","volume":"13","author":"Garmilla","year":"2012","journal-title":"Curr. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1756-8935-6-24","article-title":"Proteomic characterization of novel histone post-translational modifications","volume":"6","author":"Arnaudo","year":"2013","journal-title":"Epigenet. Chromatin"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cell.2014.09.037","article-title":"SnapShot: Histone modifications","volume":"159","author":"Huang","year":"2014","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19915","DOI":"10.1073\/pnas.1009023107","article-title":"Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code","volume":"107","author":"Sakabe","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrm2145","article-title":"Histone acetyltransferase complexes: One size doesn\u2019t fit all","volume":"8","author":"Lee","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.tplants.2015.07.005","article-title":"Histone acetylation enzymes coordinate metabolism and gene expression","volume":"20","author":"Shen","year":"2015","journal-title":"Trends Plant Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrm2346","article-title":"The Rpd3\/Hda1 family of lysine deacetylases: From bacteria and yeast to mice and men","volume":"9","author":"Yang","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.15252\/embr.201540945","article-title":"The interplay of histone modifications\u2014Writers that read","volume":"16","author":"Zhang","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nature04021","article-title":"An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation","volume":"437","author":"Lee","year":"2005","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.cell.2004.12.012","article-title":"Histone demethylation mediated by the nuclear amine oxidase homolog LSD1","volume":"119","author":"Shi","year":"2004","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0065-3233(04)67008-2","article-title":"Posttranslational modifications of histones by methylation","volume":"67","author":"Wood","year":"2004","journal-title":"Adv. Protein Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.molcel.2011.03.022","article-title":"When signaling kinases meet histones and histone modifiers in the nucleus","volume":"42","author":"Baek","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fonc.2012.00026","article-title":"Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer","volume":"2","author":"Cao","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm1963","article-title":"Poly(ADP-ribose): Novel functions for an old molecule","volume":"7","author":"Schreiber","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1073\/pnas.51.5.786","article-title":"Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis","volume":"51","author":"Allfrey","year":"1964","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1073\/pnas.55.4.805","article-title":"RNA synthesis and histone acetylation during the course of gene activation in lymphocytes","volume":"55","author":"Pogo","year":"1966","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/jcb.20217","article-title":"Regulation of RANKL promoter activity is associated with histone remodeling in murine bone stromal cells","volume":"93","author":"Fan","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2009.09.025","article-title":"Trichostatin A inhibits osteoclastogenesis and bone resorption by suppressing the induction of c-Fos by RANKL","volume":"623","author":"Kim","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"28329","DOI":"10.1074\/jbc.M115.657825","article-title":"Epigenetic Control of the Bone-master Runx2 Gene during Osteoblast-lineage Commitment by the Histone Demethylase JARID1B\/KDM5B","volume":"290","author":"Rojas","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1210\/me.2006-0061","article-title":"Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation","volume":"20","author":"Lee","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1126\/science.1105136","article-title":"The ENCODE (ENCyclopedia Of DNA Elements) Project","volume":"306","author":"Consortium","year":"2004","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng.3192","article-title":"The landscape of long noncoding RNAs in the human transcriptome","volume":"47","author":"Iyer","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrg2521","article-title":"Long non-coding RNAs: Insights into functions","volume":"10","author":"Mercer","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/epi.27473","article-title":"Non-coding RNAs as direct and indirect modulators of epigenetic regulation","volume":"9","author":"Peschansky","year":"2014","journal-title":"Epigenetics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.bbrc.2013.02.036","article-title":"Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression","volume":"432","author":"Zhu","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1080\/09168451.2014.998617","article-title":"Long non-coding RNA-DANCR in human circulating monocytes: A potential biomarker associated with postmenopausal osteoporosis","volume":"79","author":"Tong","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s00223-014-9935-7","article-title":"Analysis of the bone microRNome in osteoporotic fractures","volume":"96","author":"Sanudo","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bone.2015.05.027","article-title":"Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation","volume":"79","author":"Weilner","year":"2015","journal-title":"Bone"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/ddr.21260","article-title":"MicroRNAs in bone balance and osteoporosis","volume":"76","author":"Chen","year":"2015","journal-title":"Drug Dev. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1073\/pnas.1016758108","article-title":"MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo","volume":"108","author":"Eskildsen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/jbmr.2412","article-title":"MiR-497 approximately 195 cluster microRNAs regulate osteoblast differentiation by targeting BMP signaling","volume":"30","author":"Grunhagen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1089\/scd.2012.0014","article-title":"Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression","volume":"21","author":"Huang","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bone.2014.08.004","article-title":"MicroRNA-17\/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells","volume":"68","author":"Shi","year":"2014","journal-title":"Bone"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/15476286.2015.1017205","article-title":"miR-214 promotes osteoclastogenesis by targeting Pten\/PI3k\/Akt pathway","volume":"12","author":"Zhao","year":"2015","journal-title":"RNA Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/stem.288","article-title":"MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation","volume":"28","author":"Huang","year":"2010","journal-title":"Stem Cells"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1002\/jcp.24557","article-title":"A positive role of microRNA-15b on regulation of osteoblast differentiation","volume":"229","author":"Vimalraj","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3109\/s10165-012-0710-1","article-title":"Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation","volume":"23","author":"Shibuya","year":"2013","journal-title":"Mod. Rheumatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1038\/cdd.2015.99","article-title":"miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K\/AKT pathway","volume":"22","author":"Li","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3892\/mmr.2015.3497","article-title":"MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7","volume":"12","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bbrc.2015.03.059","article-title":"MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1","volume":"460","author":"Li","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1016\/j.febslet.2014.11.008","article-title":"miR-96 promotes osteogenic differentiation by suppressing HBEGF-EGFR signaling in osteoblastic cells","volume":"588","author":"Yang","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fgene.2015.00233","article-title":"miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1","volume":"6","author":"Gindin","year":"2015","journal-title":"Front. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3892\/etm.2015.2477","article-title":"microRNA-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2","volume":"10","author":"Du","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3892\/ijmm.2015.2275","article-title":"MicroRNA-153 suppresses the osteogenic differentiation of human mesenchymal stem cells by targeting bone morphogenetic protein receptor type II","volume":"36","author":"Cao","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/jcb.25026","article-title":"miR-124 negatively regulates osteogenic differentiation and in vivo bone formation of mesenchymal stem cells","volume":"116","author":"Qadir","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.bone.2015.07.006","article-title":"MicroRNA-183 increases osteoclastogenesis by repressing heme oxygenase-1","volume":"81","author":"Ke","year":"2015","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.bone.2014.07.004","article-title":"A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3)","volume":"67","author":"Liu","year":"2014","journal-title":"Bone"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"75","DOI":"10.14348\/molcells.2015.2241","article-title":"MicroRNA-26a regulates RANKL-induced osteoclast formation","volume":"38","author":"Kim","year":"2015","journal-title":"Mol. Cells"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.bbagrm.2014.08.002","article-title":"MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation","volume":"1839","author":"Dou","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature13375","article-title":"miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2","volume":"512","author":"Krzeszinski","year":"2014","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.bbrc.2013.12.075","article-title":"MiR-126\u20135p regulates osteoclast differentiation and bone resorption in giant cell tumor through inhibition of MMP-13","volume":"443","author":"Wu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.3390\/jcm4091741","article-title":"MicroRNAs and osteolytic bone metastasis: The roles of MicroRNAs in tumor-induced osteoclast differentiation","volume":"4","author":"Kagiya","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/jre.12017","article-title":"Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation","volume":"48","author":"Kagiya","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1080\/15476286.2014.996462","article-title":"The role of microRNAs in osteoclasts and osteoporosis","volume":"11","author":"Tang","year":"2014","journal-title":"RNA Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1002\/jcp.24679","article-title":"Pin1 regulates osteoclast fusion through suppression of the master regulator of cell fusion DC-STAMP","volume":"229","author":"Islam","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bone.2015.07.023","article-title":"Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion of pre-osteoclasts","volume":"81","author":"Kim","year":"2015","journal-title":"Bone"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jintaridth, P., Tungtrongchitr, R., Preutthipan, S., and Mutirangura, A. (2013). Hypomethylation of Alu elements in post-menopausal women with osteoporosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070386"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/jbmr.2342","article-title":"Methylation of bone SOST, its mRNA, and serum sclerostin levels correlate strongly with fracture risk in postmenopausal women","volume":"30","author":"Reppe","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, J.G., Tan, L.J., Xu, C., He, H., Tian, Q., Zhou, Y., Qiu, C., Chen, X.D., and Deng, H.W. (2015). Integrative analysis of transcriptomic and epigenomic data to reveal regulation patterns for BMD variation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138524"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jsbmb.2008.11.005","article-title":"RANKL\/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis","volume":"113","author":"Giner","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11010-011-0836-z","article-title":"Methylation of the promoter A of estrogen receptor alpha gene in hBMSC and osteoblasts and its correlation with homocysteine","volume":"355","author":"Lv","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2012.04.009","article-title":"Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs","volume":"11","author":"Ye","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/mt.2015.152","article-title":"Suppression of EZH2 prevents the shift of osteoporotic MSC fate to adipocyte and enhances bone formation during osteoporosis","volume":"24","author":"Jing","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/jbmr.2602","article-title":"Hdac3 deficiency increases marrow adiposity and induces lipid storage and glucocorticoid metabolism in osteochondroprogenitor cells","volume":"31","author":"Carpio","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/jbmr.2175","article-title":"Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures","volume":"29","author":"Seeliger","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mce.2015.10.015","article-title":"Circulating microRNAs as novel biomarkers for bone diseases\u2014Complex signatures for multifactorial diseases?","volume":"432","author":"Hackl","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e971","DOI":"10.7717\/peerj.971","article-title":"Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis","volume":"3","author":"Meng","year":"2015","journal-title":"PeerJ"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00223-015-0036-z","article-title":"Serum circulating microRNAs as biomarkers of osteoporotic fracture","volume":"97","author":"Panach","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1158\/0008-5472.CAN-10-0655","article-title":"Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34","volume":"70","author":"Wiggins","year":"2010","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.3892\/mmr.2015.3581","article-title":"Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA-338-3p","volume":"12","author":"Guo","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.molcel.2014.05.016","article-title":"The mechanisms behind the therapeutic activity of BET bromodomain inhibition","volume":"54","author":"Shi","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"24995","DOI":"10.1074\/jbc.M114.564997","article-title":"Class I and IIa histone deacetylases have opposite effects on sclerostin gene regulation","volume":"289","author":"Baertschi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/jbmr.426","article-title":"Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription","volume":"26","author":"Kim","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1038\/ncomms4511","article-title":"Selective inhibition of BET bromodomain epigenetic signalling interferes with the bone-associated tumour vicious cycle","volume":"5","author":"Lamoureux","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"24458","DOI":"10.1074\/jbc.M111.223297","article-title":"Inhibition of osteoclast differentiation and bone resorption by N-methylpyrrolidone","volume":"286","author":"Ghayor","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00011-015-0833-x","article-title":"N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-kappaB signaling","volume":"64","author":"Ghayor","year":"2015","journal-title":"Inflamm. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.bone.2015.05.004","article-title":"The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis","volume":"78","author":"Gjoksi","year":"2015","journal-title":"Bone"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Gjoksi, B., Ruangsawasdi, N., Ghayor, C., Siegenthaler, B., Zenobi-Wong, M., and Weber, F.E. (2016). Influence of N-methyl pyrrolidone on the activity of the pulp-dentine complex and bone integrity during osteoporosis. Int. Endod. J.","DOI":"10.1111\/iej.12622"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1177\/0022034514534261","article-title":"BET inhibitor JQ1 blocks inflammation and bone destruction","volume":"93","author":"Meng","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1038\/ncomms6418","article-title":"Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation","volume":"5","author":"Lim","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22203\/eCM.v028a19","article-title":"Role and regulation of Runx2 in osteogenesis","volume":"28","author":"Bruderer","year":"2014","journal-title":"Eur. Cell. Mater."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1089\/ten.tea.2009.0009","article-title":"N-methyl pyrrolidone as a potent bone morphogenetic protein enhancer for bone tissue regeneration","volume":"15","author":"Miguel","year":"2009","journal-title":"Tissue Eng. Part A"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/9\/1446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:29:53Z","timestamp":1760210993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/9\/1446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,1]]},"references-count":110,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2016,9]]}},"alternative-id":["ijms17091446"],"URL":"https:\/\/doi.org\/10.3390\/ijms17091446","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,1]]}}}