{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:54:21Z","timestamp":1789386861116,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MUR (Ministry of University and Research), Italy","award":["2020XMLP45"],"award-info":[{"award-number":["2020XMLP45"]}]},{"name":"MUR (Ministry of University and Research), Italy","award":["RM123188F1F65F5C"],"award-info":[{"award-number":["RM123188F1F65F5C"]}]},{"name":"Sapienza University of Rome, Italy","award":["2020XMLP45"],"award-info":[{"award-number":["2020XMLP45"]}]},{"name":"Sapienza University of Rome, Italy","award":["RM123188F1F65F5C"],"award-info":[{"award-number":["RM123188F1F65F5C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory\/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. In silico annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration.<\/jats:p>","DOI":"10.3390\/cells14020135","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T11:24:56Z","timestamp":1737113096000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-5103","authenticated-orcid":false,"given":"Giulia","family":"Gerini","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6138-6179","authenticated-orcid":false,"given":"Alice","family":"Traversa","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Cece","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Cassandri","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-3775","authenticated-orcid":false,"given":"Paola","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-3640","authenticated-orcid":false,"given":"Simona","family":"Camero","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Nannini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9514-6472","authenticated-orcid":false,"given":"Enrico","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-8135","authenticated-orcid":false,"given":"Mary Anna","family":"Venneri","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-7719","authenticated-orcid":false,"given":"Simona","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Angeloni","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-9343","authenticated-orcid":false,"given":"Amedeo","family":"Amedei","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, 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Bone Joint Surg. Br."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e203","DOI":"10.1097\/BOT.0000000000000034","article-title":"Evidence-Based Quality Value and Safety Committee\u2014Orthopaedic Trauma Association, Writing Committee. Current Practice in the Management of Open Fractures Among Orthopaedic Trauma Surgeons. Part B: Management of Segmental Long Bone Defects. A Survey of Orthopaedic Trauma Association Members","volume":"28","author":"Obremskey","year":"2014","journal-title":"J. Orthop. Trauma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1002\/sct3.13035","article-title":"Developing standards to support the clinical translation of stem cells","volume":"10","author":"Cao","year":"2021","journal-title":"Stem Cells Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17014","DOI":"10.1038\/boneres.2017.14","article-title":"Injectable hydrogels for cartilage and bone tissue engineering","volume":"5","author":"Liu","year":"2017","journal-title":"Bone Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Khan, M.U.A., Razak, S.I.A., Ansari, M.N.M., Zulkifli, R.M., Ahmad Zawawi, N., and Arshad, M. (2021). Development of Biodegradable Bio-Based Composite for Bone Tissue Engineering: Synthesis, Characterization and In Vitro Biocompatible Evaluation. Polymers, 13.","DOI":"10.3390\/polym13213611"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1091\/mbc.e02-02-0105","article-title":"Human adipose tissue is a source of multipotent stem cells","volume":"13","author":"Zuk","year":"2002","journal-title":"Mol. Biol. Cell."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Al-Ghadban, S., Artiles, M., and Bunnell, B.A. (2022). Adipose Stem Cells in Regenerative Medicine: Looking Forward. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.837464"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/scrt328","article-title":"Effects of dexamethasone, ascorbic acid and \u03b2-glycerophosphate on the osteogenic differentiation of stem cells in vitro","volume":"4","author":"Langenbach","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Brito Barrera, Y.A., Husteden, C., Alherz, J., Fuhrmann, B., W\u00f6lk, C., and Groth, T. (2021). Extracellular matrix-inspired surface coatings functionalized with dexamethasone-loaded liposomes to induce osteo- and chondrogenic differentiation of multipotent stem cells. Mater. Sci. Eng. C Mater. Biol. Appl., 131.","DOI":"10.1016\/j.msec.2021.112516"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/08941939.2019.1604915","article-title":"A New Procedure in Bone Engineering Using Induced Adipose Tissue","volume":"34","author":"Alfotawi","year":"2021","journal-title":"J. Investig. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1177\/0963689719880527","article-title":"Autologous Micro-Fragmented Adipose Tissue as Stem Cell-Based Natural Scaffold for Cartilage Defect Repair","volume":"28","author":"Xu","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Yang, X., Cao, X., Qin, A., and Zhao, J. (2022). Current applications of adipose-derived mesenchymal stem cells in bone repair and regeneration: A review of cell experiments, animal models, and clinical trials. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.942128"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1016\/j.biochi.2013.06.001","article-title":"Review of the adipose derived stem cell secretome","volume":"95","author":"Kapur","year":"2013","journal-title":"Biochimie"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"574","DOI":"10.2174\/156652412800619950","article-title":"Immunosuppressive properties of mesenchymal stem cells: Advances and applications","volume":"12","author":"Pascual","year":"2012","journal-title":"Curr. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Calabrese, G., Giuffrida, R., Forte, S., Fabbi, C., Figallo, E., Salvatorelli, L., Memeo, L., Parenti, R., Gulisano, M., and Gulino, R. (2017). Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-07672-0"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hutton, D.L., Kondragunta, R., Moore, E.M., Hung, B.P., Jia, X., and Grayson, W.L. (2014). Tumor necrosis factor improves vascularization in osteogenic grafts engineered with human adipose-derived stem\/stromal cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107199"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41434-022-00367-w","article-title":"Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential","volume":"30","author":"Collon","year":"2023","journal-title":"Gene Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1002\/jcp.24965","article-title":"In Vitro evaluation of different methods of handling human liposuction aspirate and their effect on adipocytes and adipose derived stem cells","volume":"230","author":"Palumbo","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1038\/emm.2014.28","article-title":"Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human adipose tissue mesenchymal stem cells","volume":"46","author":"Han","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/sctm.19-0234","article-title":"The influence of fibroblast growth factor 2 on the senescence of human adipose-derived mesenchymal stem cells during long-term culture","volume":"9","author":"Cheng","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ceccarelli, S., Gerini, G., Megiorni, F., Pontecorvi, P., Messina, E., Camero, S., Anastasiadou, E., Romano, E., Onesti, M.G., and Napoli, C. (2022). Inhibiting DNA methylation as a strategy to enhance adipose-derived stem cells differentiation: Focus on the role of Akt\/mTOR and Wnt\/\u03b2-catenin pathways on adipogenesis. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.926180"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6305","DOI":"10.1158\/0008-5472.CAN-04-2957","article-title":"Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases","volume":"65","author":"Brueckner","year":"2005","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00395-015-0528-z","article-title":"DNA methylation in an engineered heart tissue model of cardiac hypertrophy: Common signatures and effects of DNA methylation inhibitors","volume":"111","author":"Stenzig","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Assis, R.I.F., Wiench, M., Silverio, K.G., da Silva, R.A., da Silva Feltran, G., Sallum, E.A., Casati, M.Z., Nociti, F.H., and Andia, D.C. (2018). RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207873"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1075156","DOI":"10.1155\/2018\/1075156","article-title":"Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis","volume":"2018","author":"Ceccarelli","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.canlet.2020.03.011","article-title":"BET inhibition therapy counteracts cancer cell survival, clonogenic potential and radioresistance mechanisms in rhabdomyosarcoma cells","volume":"479","author":"Camero","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e415","DOI":"10.5301\/ijbm.5000284","article-title":"EpCAM-expressing circulating tumor cells in colorectal cancer","volume":"32","author":"Nicolazzo","year":"2017","journal-title":"Int. J. Biol. Markers"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D882","DOI":"10.1093\/nar\/gkz1062","article-title":"New developments on the Encyclopedia of DNA Elements (ENCODE) data portal","volume":"48","author":"Luo","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9919361","DOI":"10.1155\/2021\/9919361","article-title":"An In Vitro and In Vivo Comparison of Osteogenic Differentiation of Human Mesenchymal Stromal\/Stem Cells","volume":"2021","author":"Mollentze","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ye, J., Xiao, J., Wang, J., Ma, Y., Zhang, Y., Zhang, Q., Zhang, Z., and Yin, H. (2022). The Interaction Between Intracellular Energy Metabolism and Signaling Pathways During Osteogenesis. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.807487"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1210\/me.2008-0270","article-title":"The osteogenic transcription factor runx2 controls genes involved in sterol\/steroid metabolism, including CYP11A1 in osteoblasts","volume":"23","author":"Teplyuk","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bbagrm.2013.11.005","article-title":"Transcriptional regulation of human ferredoxin reductase through an intronic enhancer in steroidogenic cells","volume":"1839","author":"Imamichi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e1800311","DOI":"10.1002\/pmic.201800311","article-title":"GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis","volume":"19","author":"Forcina","year":"2019","journal-title":"Proteomics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lungu, O., Toscani, D., Burroughs-Garcia, J., and Giuliani, N. (2023). The Metabolic Features of Osteoblasts: Implications for Multiple Myeloma (MM) Bone Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054893"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kasprzak, A. (2021). Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126434"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhao, L., Liu, S., Peng, Y., and Zhang, J. (2024). Lamc1 promotes osteogenic differentiation and inhibits adipogenic differentiation of bone marrow-derived mesenchymal stem cells. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-69629-4"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12925","DOI":"10.1074\/jbc.M109.061754","article-title":"Insulin-like growth factor-binding protein-5-induced laminin gamma1 transcription requires filamin A","volume":"285","author":"Abrass","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13287-018-0798-0","article-title":"Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin \u03b15","volume":"9","author":"Sun","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/s42255-023-00774-2","article-title":"Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions","volume":"5","author":"Skinner","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41551-019-0422-3","article-title":"Retinoic-acid-induced osteogenesis of hiPSCs","volume":"3","author":"Jacobsen","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1097\/PRS.0b013e3181d62980","article-title":"Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells: Potential mechanisms of retinoid-induced craniosynostosis","volume":"125","author":"James","year":"2010","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s10142-024-01465-1","article-title":"ALDH2 alleviates inflammation and facilitates osteogenic differentiation of periodontal ligament stem cells in periodontitis by blocking ferroptosis via activating Nrf2","volume":"24","author":"Chen","year":"2024","journal-title":"Funct. Integr. Genom."},{"key":"ref_46","first-page":"492","article-title":"The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis","volume":"18","author":"Li","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tang, C.Y., Wu, M., Zhao, D., Edwards, D., McVicar, A., Luo, Y., Zhu, G., Wang, Y., Zhou, H.D., and Chen, W. (2021). Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009233"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Komori, T. (2024). Regulation of Skeletal Development and Maintenance by Runx2 and Sp7. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810102"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1074\/jbc.M110.152900","article-title":"Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2","volume":"286","author":"Saito","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/03008207.2017.1313248","article-title":"MAPK signaling has stage-dependent osteogenic effects on human adipose-derived stem cells in vitro","volume":"59","author":"Tsang","year":"2018","journal-title":"Connect. Tissue Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Damerau, A., Gaber, T., Ohrndorf, S., and Hoff, P. (2020). JAK\/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239004"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sun, L., Ma, J., Chen, J., Pan, Z., and Li, L. (2022). Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.800288"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.bone.2009.10.024","article-title":"Osteo-transcriptomics of human mesenchymal stem cells: Accelerated gene expression and osteoblast differentiation induced by vitamin D reveals c-MYC as an enhancer of BMP2-induced osteogenesis","volume":"46","author":"Piek","year":"2010","journal-title":"Bone"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1080\/15384101.2021.1985772","article-title":"TAp63 regulates bone remodeling by modulating the expression of TNFRSF11B\/Osteoprotegerin","volume":"20","author":"Lena","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00223-016-0219-2","article-title":"Osteogenic Potential of the Transcription Factor c-MYB","volume":"100","author":"Oralova","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/jbmr.294","article-title":"Unique roles of phosphorus in endochondral bone formation and osteocyte maturation","volume":"26","author":"Zhang","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.cellsig.2016.06.004","article-title":"AMPK promotes osteogenesis and inhibits adipogenesis through AMPK-Gfi1-OPN axis","volume":"28","author":"Wang","year":"2016","journal-title":"Cell Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"103010","DOI":"10.1016\/j.scr.2022.103010","article-title":"PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis","volume":"66","author":"Gao","year":"2023","journal-title":"Stem Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s10495-023-01820-w","article-title":"IRF-1-inhibited lncRNA XIST regulated the osteogenic differentiation via miR-450b\/FBXW7 axis","volume":"28","author":"Song","year":"2023","journal-title":"Apoptosis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.humimm.2009.02.002","article-title":"Antibodies against HLA-DQ alpha-chain and their role in organ transplantation","volume":"70","author":"Barabanova","year":"2009","journal-title":"Hum. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/sctm.18-0266","article-title":"Adipose-Derived Stromal Cells Are Capable of Restoring Bone Regeneration After Post-Traumatic Osteomyelitis and Modulate B-Cell Response","volume":"8","author":"Wagner","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Freitas, G.P., Souza, A.T.P., Lopes, H.B., Trevisan, R.L.B., Oliveira, F.S., Fernandes, R.R., Ferreira, F.U., Ros, F.A., Beloti, M.M., and Rosa, A.L. (2020). Mesenchymal Stromal Cells Derived from Bone Marrow and Adipose Tissue: Isolation, Culture, Characterization and Differentiation. Bio. Protoc., 10.","DOI":"10.21769\/BioProtoc.3534"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s44324-024-00010-9","article-title":"Bone metabolism\u2014An underappreciated player","volume":"2","author":"Choi","year":"2024","journal-title":"NPJ Metab. Health Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sheppard, A.J., Barfield, A.M., Barton, S., and Dong, Y. (2022). Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.836764"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1634\/stemcells.2007-0509","article-title":"Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells","volume":"26","author":"Chen","year":"2008","journal-title":"Stem Cells"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.7150\/thno.99237","article-title":"Hypoxia inducible factor (HIF) 3\u03b1 prevents COPD by inhibiting alveolar epithelial cell ferroptosis via the HIF-3\u03b1-GPx4 axis","volume":"14","author":"Jiang","year":"2024","journal-title":"Theranostics"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Qin, Q., Liu, Y., Yang, Z., Aimaijiang, M., Ma, R., Yang, Y., Zhang, Y., and Zhou, Y. (2022). Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911201"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/stmcls\/sxac042","article-title":"Epigenetic Regulation of NGF-Mediated Osteogenic Differentiation in Human Dental Mesenchymal Stem Cells","volume":"40","author":"Liu","year":"2022","journal-title":"Stem Cells"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1089\/dna.2020.6239","article-title":"DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells","volume":"40","author":"Assis","year":"2021","journal-title":"DNA Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1089\/cell.2019.0060","article-title":"Inhibition of DNA Methyltransferase by RG108 Promotes Pluripotency-Related Character of Porcine Bone Marrow Mesenchymal Stem Cells","volume":"22","author":"Li","year":"2020","journal-title":"Cell. Reprogram."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/bab.1393","article-title":"Anti-senescence effects of DNA methyltransferase inhibitor RG108 in human bone marrow mesenchymal stromal cells","volume":"62","author":"Oh","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4824209","DOI":"10.1155\/2019\/4824209","article-title":"Dnmt3a-Mediated DNA Methylation Changes Regulate Osteogenic Differentiation of hMSCs Cultivated in the 3D Scaffolds under Oxidative Stress","volume":"2019","author":"Li","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1158\/0008-5472.CAN-05-2821","article-title":"Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines","volume":"66","author":"Stresemann","year":"2006","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"488","DOI":"10.22203\/eCM.v021a37","article-title":"Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells","volume":"21","author":"Janicki","year":"2011","journal-title":"Eur. Cells Mater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1093\/jnci\/dji311","article-title":"DNA methyltransferase inhibitors and the development of epigenetic cancer therapies","volume":"97","author":"Lyko","year":"2005","journal-title":"J. Natl. Cancer Inst."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:08Z","timestamp":1759919468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/2\/135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":75,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14020135"],"URL":"https:\/\/doi.org\/10.3390\/cells14020135","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]}}}