{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:25:06Z","timestamp":1791822306794,"version":"4.3.4"},"reference-count":108,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone turnover is sophisticatedly balanced by a dynamic coupling of bone formation and resorption at various rates. The orchestration of this continuous remodeling of the skeleton further affects other skeletal tissues through organ crosstalk. Chronic excessive bone resorption compromises bone mass and its porous microstructure as well as proper biomechanics. This accelerates the development of osteoporotic disorders, a leading cause of skeletal degeneration-associated disability and premature death. Bone-forming cells play important roles in maintaining bone deposit and osteoclastic resorption. A poor organelle machinery, such as mitochondrial dysfunction, endoplasmic reticulum stress, and defective autophagy, etc., dysregulates growth factor secretion, mineralization matrix production, or osteoclast-regulatory capacity in osteoblastic cells. A plethora of epigenetic pathways regulate bone formation, skeletal integrity, and the development of osteoporosis. MicroRNAs inhibit protein translation by binding the 3\u2032-untranslated region of mRNAs or promote translation through post-transcriptional pathways. DNA methylation and post-translational modification of histones alter the chromatin structure, hindering histone enrichment in promoter regions. MicroRNA-processing enzymes and DNA as well as histone modification enzymes catalyze these modifying reactions. Gain and loss of these epigenetic modifiers in bone-forming cells affect their epigenetic landscapes, influencing bone homeostasis, microarchitectural integrity, and osteoporotic changes. This article conveys productive insights into biological roles of DNA methylation, microRNA, and histone modification and highlights their interactions during skeletal development and bone loss under physiological and pathological conditions.<\/jats:p>","DOI":"10.3390\/ijms21144923","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Epigenetic Regulation of Skeletal Tissue Integrity and Osteoporosis Development"],"prefix":"10.3390","volume":"21","author":[{"given":"Yu-Shan","family":"Chen","sequence":"first","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shiung","family":"Lian","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Jing","family":"Ke","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Chen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7308-5584","authenticated-orcid":false,"given":"Holger","family":"Jahr","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"Department of Orthopedic Surgery, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"US Preventive Services Task Force, Grossman, D.C., Curry, S.J., Owens, U.K., Barry, M.J., Caughey, A.B., Davidson, K.W., Doubeni, C.A., Epling, J.W., and Kemper, A.R. (2018). Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement. JAMA, 319, 1696\u20131704.","DOI":"10.1001\/jama.2018.3097"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S2213-8587(18)30026-3","article-title":"The physiology of endocrine systems with ageing","volume":"6","author":"Kaufman","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1056\/NEJMra1402513","article-title":"The Key Role of Epigenetics in Human Disease Prevention and Mitigation","volume":"378","author":"Feinberg","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41580-019-0136-0","article-title":"The roles of structural dynamics in the cellular functions of RNAs","volume":"20","author":"Ganser","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrg.2017.80","article-title":"The DNA methyltransferase family: A versatile toolkit for epigenetic regulation","volume":"19","author":"Lyko","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41580-019-0143-1","article-title":"The roles of DNA, RNA and histone methylation in ageing and cancer","volume":"20","author":"Michalak","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature14192","article-title":"Function and information content of DNA methylation","volume":"517","year":"2015","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1172\/JCI84424","article-title":"Targeting noncoding RNAs in disease","volume":"127","author":"Adams","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00018-018-2940-7","article-title":"Regulatory network of miRNA on its target: Coordination between transcriptional and post-transcriptional regulation of gene expression","volume":"76","author":"Pu","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41591-019-0376-8","article-title":"Targeting epigenetic modifications in cancer therapy: Erasing the roadmap to cancer","volume":"25","author":"Mohammad","year":"2019","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Piunti, A., and Shilatifard, A. (2016). Epigenetic balance of gene expression by Polycomb and COMPASS families. Science, 352.","DOI":"10.1126\/science.aad9780"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nm.4036","article-title":"Targeting EZH2 in cancer","volume":"22","author":"Kim","year":"2016","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrm.2016.140","article-title":"Metabolic regulation of gene expression through histone acylations","volume":"18","author":"Sabari","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41574-019-0282-7","article-title":"A road map for understanding molecular and genetic determinants of osteoporosis","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41574-020-0335-y","article-title":"The role of cellular senescence in ageing and endocrine disease","volume":"16","author":"Khosla","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nrendo.2016.153","article-title":"Mechanisms of diabetes mellitus-induced bone fragility","volume":"13","author":"Napoli","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1002\/jbmr.3564","article-title":"The Spectrum of Fundamental Basic Science Discoveries Contributing to Organismal Aging","volume":"33","author":"Farr","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eaaw7215","DOI":"10.1126\/sciadv.aaw7215","article-title":"Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network","volume":"5","author":"Gao","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Suzuki, R., Fujiwara, Y., Saito, M., Arakawa, S., Shirakawa, J., Yamanaka, M., Komohara, Y., Marumo, K., and Nagai, R. (2020). Intracellular accumulation of advanced glycation end-products induces osteoblast apoptosis via endoplasmic reticulum stress. J. Bone Miner. Res.","DOI":"10.1002\/jbmr.4053"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eaax0672","DOI":"10.1126\/sciadv.aax0672","article-title":"Osteoblastic lysosome plays a central role in mineralization","volume":"5","author":"Iwayama","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1002\/jbmr.3563","article-title":"The Lysosomal Protein Arylsulfatase B is a Key Enzyme Involved in Skeletal Turnover","volume":"33","author":"Pohl","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1205406","article-title":"Autophagy in human health and disease","volume":"368","author":"Choi","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/nm.3288","article-title":"Autophagy regulates endothelial cell processing, maturation and secretion of von Willebrand factor","volume":"19","author":"Torisu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/nm.4222","article-title":"Cardioprotection and lifespan extension by the natural polyamine spermidine","volume":"22","author":"Eisenberg","year":"2016","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12105","DOI":"10.1002\/jcp.27071","article-title":"Autophagy plays an essential role in bone homeostasis","volume":"234","author":"Jaber","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.4161\/auto.36182","article-title":"Autophagy in osteoblasts is involved in mineralization and bone homeostasis","volume":"10","author":"Nollet","year":"2014","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1080\/15548627.2018.1483807","article-title":"Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss","volume":"14","author":"Li","year":"2018","journal-title":"Autophagy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1038\/s41467-019-11373-9","article-title":"Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone","volume":"10","author":"Vrahnas","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12709","DOI":"10.1111\/acel.12709","article-title":"Autophagy controls mesenchymal stem cell properties and senescence during bone aging","volume":"17","author":"Ma","year":"2017","journal-title":"Aging Cell"},{"key":"ref_32","first-page":"1","article-title":"NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis","volume":"10","author":"Zhao","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s41419-018-0970-6","article-title":"Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid aggravation of osteoporosis by chaperoning RPTOR","volume":"9","author":"Lian","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00109-016-1422-3","article-title":"Chaperonin 60 regulation of SOX9 ubiquitination mitigates the development of knee osteoarthritis","volume":"94","author":"Ko","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jbmr.3662","article-title":"Role of Epigenomics in Bone and Cartilage Disease","volume":"34","author":"Boer","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tig.2018.10.004","article-title":"Dissecting the Genetics of Osteoporosis using Systems Approaches","volume":"35","author":"Farber","year":"2019","journal-title":"Trends Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nrrheum.2016.48","article-title":"The genetics of bone mass and susceptibility to bone diseases","volume":"12","author":"Karasik","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bellavia, D., Costa, V., De Luca, A., Maglio, M., Pagani, S., Fini, M., and Giavaresi, G. (2016). Vitamin D Level between Calcium-Phosphorus Homeostasis and Immune System: New Perspective in Osteoporosis. Curr. Osteoporos. Rep.","DOI":"10.1007\/s11914-016-0331-2"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1136\/annrheumdis-2017-212469","article-title":"Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density","volume":"77","author":"Alonso","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","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\u2013producing metabolic pathway","volume":"21","author":"Nishikawa","year":"2015","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1038\/s41467-018-04464-6","article-title":"Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter","volume":"9","author":"Yang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1002\/jbmr.3527","article-title":"Identification of an epigenetic signature of osteoporosis in blood DNA of postmenopausal women","volume":"33","author":"Cheishville","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1080\/15592294.2017.1345832","article-title":"Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women","volume":"12","author":"Reppe","year":"2017","journal-title":"Epigenetics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/jbmr.2342","article-title":"Methylation of BoneSOST, 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_45","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1038\/s41467-019-12525-7","article-title":"Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression","volume":"10","author":"Nicolle","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13045-017-0465-4","article-title":"An imprinted non-coding genomic cluster at 14q32 defines clinically relevant molecular subtypes in osteosarcoma across multiple independent datasets","volume":"10","author":"Hill","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20046","DOI":"10.1038\/srep20046","article-title":"Involvement of MicroRNA-210 demethylation in dteroid-associated dsteonecrosis of the femoral head","volume":"6","author":"Yuan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41580-019-0106-6","article-title":"Publisher Correction: Regulation of microRNA biogenesis and its crosstalk with other cellular pathways","volume":"20","author":"Treiber","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI87316","article-title":"Extracellular vesicles: Masters of intercellular communication and potential clinical interventions","volume":"126","author":"Pitt","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.7150\/thno.42640","article-title":"RNA-based scaffolds for bone regeneration: Application and mechanisms of mRNA, miRNA and siRNA","volume":"10","author":"Leng","year":"2020","journal-title":"Theranostics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bone.2017.10.018","article-title":"Dicer1 ablation in osterix positive bone forming cells affects cortical bone homeostasis","volume":"106","author":"Bendre","year":"2018","journal-title":"Bone"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bone.2017.07.021","article-title":"Deficiency of DGCR8 increases bone formation through downregulation of miR-22 expression","volume":"103","author":"Choi","year":"2017","journal-title":"Bone"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"32112","DOI":"10.1038\/srep32112","article-title":"Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.joca.2015.02.015","article-title":"Early postnatal ablation of the microRNA-processing enzyme, Drosha, causes chondrocyte death and impairs the structural integrity of the articular cartilage","volume":"23","author":"Kobayashi","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1002\/jbmr.3832","article-title":"MiR-146a Deletion Protects from Bone Loss in OVX Mice by Suppressing RANKL\/OPG and M-CSF in Bone Microenvironment","volume":"34","author":"Zhao","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41419-019-1428-1","article-title":"Mmu-miR-185 depletion promotes osteogenic differentiation and suppresses bone loss in osteoporosis through the Bgn-mediated BMP\/Smad pathway","volume":"10","author":"Cui","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16003","DOI":"10.1038\/ncomms16003","article-title":"MiR-497\u223c195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1\u03b1 activity","volume":"8","author":"Yang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1172\/JCI77716","article-title":"MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation","volume":"125","author":"Li","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.7150\/thno.42982","article-title":"miR-128 plays a critical role in murine osteoclastogenesis and estrogen deficiency-induced bone loss","volume":"10","author":"Shen","year":"2020","journal-title":"Theranostics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10872","DOI":"10.1038\/ncomms10872","article-title":"Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation","volume":"7","author":"Li","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.7150\/thno.34493","article-title":"Circulating miR-338 Cluster activities on osteoblast differentiation: Potential Diagnostic and Therapeutic Targets for Postmenopausal Osteoporosis","volume":"9","author":"Lin","year":"2019","journal-title":"Theranostics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1038\/s41598-018-26525-y","article-title":"Circulating microRNAs as potential diagnostic biomarkers for osteoporosis","volume":"8","author":"Mandourah","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"115105","DOI":"10.1016\/j.bone.2019.115105","article-title":"Serum microRNAs as novel biomarkers for osteoporotic vertebral fractures","volume":"130","author":"Zarecki","year":"2019","journal-title":"Bone"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Pickering, M.-E., Millet, M., Rousseau, J.-C., Croset, M., Szulc, P., Borel, O., Rendu, E.S., and Chapurlat, R. (2019). Selected serum microRNA, abdominal aortic calcification and risk of osteoporotic fracture. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216947"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1210\/jc.2017-02585","article-title":"Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling","volume":"103","author":"Hackl","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1210\/jc.2017-02406","article-title":"Changes of Circulating MicroRNAs in Response to Treatment with Teriparatide or Denosumab in Postmenopausal Osteoporosis","volume":"103","author":"Anastasilakis","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/s41467-019-09860-0","article-title":"GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures","volume":"10","author":"Styrkarsdottir","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_68","first-page":"2940","article-title":"Identification of differentially expressed microRNAs in the bone marrow of osteoporosis patients","volume":"11","author":"Gu","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/jbmr.3974","article-title":"Distinct Subsets of Noncoding RNAs Are Strongly Associated with BMD and Fracture, Studied in Weight-Bearing and Non\u2013Weight-Bearing Human Bone","volume":"35","author":"Gautvik","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1152\/physiolgenomics.00141.2011","article-title":"The miR-29 family: Genomics, cell biology, and relevance to renal and cardiovascular injury","volume":"44","author":"Kriegel","year":"2012","journal-title":"Physiol. Genom."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1002\/art.37948","article-title":"MicroRNA-29a Protects Against Glucocorticoid-Induced Bone Loss and Fragility in Rats by Orchestrating Bone Acquisition and Resorption","volume":"65","author":"Wang","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bone.2015.06.022","article-title":"MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation","volume":"81","author":"Ko","year":"2015","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41419-019-1942-1","article-title":"MicroRNA-29a represses osteoclast formation and protects against osteoporosis by regulating PCAF-mediated RANKL and CXCL12","volume":"10","author":"Lian","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00109-015-1374-z","article-title":"The microRNA-29 family in cartilage homeostasis and osteoarthritis","volume":"94","author":"Le","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/rheumatology\/kez195","article-title":"Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sj\u00f6gren\u2019s syndrome is associated with processes at the centre of their function","volume":"58","author":"Hillen","year":"2019","journal-title":"Rheumatology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1007\/s00018-017-2456-6","article-title":"Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice","volume":"74","author":"Dooley","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1038\/s41467-018-05187-4","article-title":"SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7\/Osterix","volume":"9","author":"Fukuda","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1002\/stem.2424","article-title":"Histone H3K9 Acetyltransferase PCAF Is Essential for Osteogenic Differentiation Through Bone Morphogenetic Protein Signaling and May Be Involved in Osteoporosis","volume":"34","author":"Zhang","year":"2016","journal-title":"Stem Cells"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/jbmr.2704","article-title":"Histone Acetyltransferase GCN5 Regulates Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting NF-\u03baB","volume":"31","author":"Zhang","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-017-0231-0","article-title":"Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis","volume":"9","author":"Jing","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1002\/jbmr.3236","article-title":"Histone Deacetylase 3 Deletion in Mesenchymal Progenitor Cells Hinders Long Bone Development","volume":"32","author":"Feigenson","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_82","first-page":"116","article-title":"Hdac3 Deficiency Increases Marrow Adiposity and Induces Lipid Storage and Glucocorticoid Metabolism in Osteochondroprogenitor Cells","volume":"31","author":"Carpio","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/physrev.00004.2015","article-title":"Histone Deacetylases in Bone Development and Skeletal Disorders","volume":"95","author":"Bradley","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1172\/JCI130126","article-title":"Salt-inducible kinases dictate parathyroid hormone 1 receptor action in bone development and remodeling","volume":"129","author":"Nishimori","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/jbmr.2381","article-title":"HDAC5 controls MEF2C-driven sclerostin expression in osteocytes","volume":"30","author":"Wein","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1074\/jbc.M114.596247","article-title":"Histone Deacetylase 7 (Hdac7) Suppresses Chondrocyte Proliferation and \u03b2-Catenin Activity during Endochondral Ossification","volume":"290","author":"Bradley","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1038\/s41467-018-04679-7","article-title":"Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin","volume":"9","author":"Stegen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"115361","DOI":"10.1016\/j.bone.2020.115361","article-title":"Sirtuin 1 deficiency decreases bone mass and increases bone marrow adiposity in a mouse model of chronic energy deficiency","volume":"136","author":"Louvet","year":"2020","journal-title":"Bone"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"19001","DOI":"10.1074\/jbc.RA118.003909","article-title":"Loss of histone methyltransferase Ezh2 stimulates an osteogenic transcriptional program in chondrocytes but does not affect cartilage development","volume":"293","author":"Camilleri","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"13685","DOI":"10.1038\/ncomms13685","article-title":"EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy","volume":"7","author":"Lui","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"12894","DOI":"10.1074\/jbc.RA118.002983","article-title":"Enhancer of zeste homolog 2 (Ezh2) controls bone formation and cell cycle progression during osteogenesis in mice","volume":"293","author":"Dudakovic","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13148-018-0526-8","article-title":"Loss of maternal EED results in postnatal overgrowth","volume":"10","author":"Prokopuk","year":"2018","journal-title":"Clin. Epigenetics"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Wang, L., Niu, N., Li, L., Shao, R., Ouyang, H., and Zou, W. (2018). H3K36 trimethylation mediated by SETD2 regulates the fate of bone marrow mesenchymal stem cells. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006522"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/stem.1573","article-title":"EZH2 and KDM6A act as an epigenetic switch to regulate mesenchymal stem cell lineage specification","volume":"32","author":"Hemming","year":"2014","journal-title":"Stem Cells"},{"key":"ref_95","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_96","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1096\/fj.201900154RR","article-title":"Histone Lys demethylase KDM3C demonstrates anti-inflammatory effects by suppressing NF-\u03baB signaling and osteoclastogenesis","volume":"33","author":"Lee","year":"2019","journal-title":"FASEB J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e2335","DOI":"10.1038\/cddis.2016.238","article-title":"KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of bone mesenchymal stem cells during osteoporosis","volume":"7","author":"Wang","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00109-017-1512-x","article-title":"Histone demethylase UTX counteracts glucocorticoid deregulation of osteogenesis by modulating histone-dependent and -independent pathways","volume":"95","author":"Wang","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.omtn.2019.12.020","article-title":"Inhibition of CRY2 by STAT3\/miRNA-7-5p Promotes Osteoblast Differentiation through Upregulation of CLOCK\/BMAL1\/P300 Expression","volume":"19","author":"Tang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17646","DOI":"10.1074\/jbc.RA118.003052","article-title":"The microRNA-23a cluster regulates the developmental HoxA cluster function during osteoblast differentiation","volume":"293","author":"Godfrey","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1111\/jcmm.13490","article-title":"MicroRNA-99a is a novel regulator of KDM6B-mediated osteogenic differentiation of BMSCs","volume":"22","author":"Tang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00109-017-1583-8","article-title":"Subchondral mesenchymal stem cells from osteoarthritic knees display high osteogenic differentiation capacity through microRNA-29a regulation of HDAC4","volume":"95","author":"Lian","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.bone.2013.09.019","article-title":"MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating \u03b2-catenin acetylation","volume":"57","author":"Ko","year":"2013","journal-title":"Bone"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.omtm.2020.04.010","article-title":"Bone-Targeting AAV-Mediated Gene Silencing in Osteoclasts for Osteoporosis Therapy","volume":"17","author":"Yang","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.omtn.2019.01.002","article-title":"MicroRNA-672-5p Identified during Weaning Reverses Osteopenia and Sarcopenia in Ovariectomized Mice","volume":"14","author":"Ahmad","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41419-017-0040-5","article-title":"The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis","volume":"9","author":"Gao","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_107","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_108","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bone.2018.03.017","article-title":"Overexpression of DNMT1 leads to hypermethylation of H19 promoter and inhibition of Erk signaling pathway in disuse osteoporosis","volume":"111","author":"Li","year":"2018","journal-title":"Bone"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:34Z","timestamp":1760176234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,12]]},"references-count":108,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21144923"],"URL":"https:\/\/doi.org\/10.3390\/ijms21144923","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,12]]}}}