{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:10:10Z","timestamp":1792523410189,"version":"4.5.0"},"reference-count":190,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["GRF17128817"],"award-info":[{"award-number":["GRF17128817"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["6173656"],"award-info":[{"award-number":["6173656"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX\/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.<\/jats:p>","DOI":"10.3390\/ijms22115445","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"5445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":246,"title":["Regulation and Role of Transcription Factors in Osteogenesis"],"prefix":"10.3390","volume":"22","author":[{"given":"Wilson Cheuk Wing","family":"Chan","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Department of Orthopaedics Surgery and Traumatology, The University of Hong Kong-Shenzhen Hospital (HKU-SZH), Shenzhen 518053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-5169","authenticated-orcid":false,"given":"Zhijia","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Surgery and Traumatology, The University of Hong Kong-Shenzhen Hospital (HKU-SZH), Shenzhen 518053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Kai Tsun","family":"To","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Surgery and Traumatology, The University of Hong Kong-Shenzhen Hospital (HKU-SZH), Shenzhen 518053, China"},{"name":"Department of Orthopaedics Surgery and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Department of Orthopaedics Surgery and Traumatology, The University of Hong Kong-Shenzhen Hospital (HKU-SZH), Shenzhen 518053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000493106","article-title":"The Osteogenic Potential of the Neural Crest Lineage May Contribute to Craniosynostosis","volume":"10","author":"Doro","year":"2019","journal-title":"Mol. Syndromol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1359\/jbmr.091116","article-title":"Origin matters: Differences in embryonic tissue origin and Wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones","volume":"25","author":"Quarto","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1002\/dvdy.20833","article-title":"Recent advances in craniofacial morphogenesis","volume":"235","author":"Chai","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bone.2015.04.035","article-title":"Bone development","volume":"80","author":"Berendsen","year":"2015","journal-title":"Bone"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"He, J., Yan, J., Wang, J., Zhao, L., Xin, Q., Zeng, Y., Sun, Y., Zhang, H., Bai, Z., and Li, Z. (2021). Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses. Cell Res.","DOI":"10.1101\/2020.12.22.423948"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/wdev.8","article-title":"Neural crest specification: Tissues, signals, and transcription factors","volume":"1","author":"Rogers","year":"2012","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ydbio.2010.04.007","article-title":"Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head","volume":"343","author":"Roybal","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ydbio.2009.04.034","article-title":"Requirement for Twist1 in frontonasal and skull vault development in the mouse embryo","volume":"331","author":"Bildsoe","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1387\/ijdb.170051gc","article-title":"Contribution of cranial neural crest cells to mouse skull development","volume":"61","author":"Wu","year":"2017","journal-title":"Int. J. Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115657","DOI":"10.1016\/j.bone.2020.115657","article-title":"JAGGED1 stimulates cranial neural crest cell osteoblast commitment pathways and bone regeneration independent of canonical NOTCH signaling","volume":"143","author":"Kamalakar","year":"2021","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Joung, Y.H., Lim, E.J., Darvin, P., Chung, S.C., Jang, J.W., Do Park, K., Lee, H.K., Kim, H.S., Park, T., and Yang, Y.M. (2012). MSM enhances GH signaling via the Jak2\/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047477"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0092-8674(00)80259-7","article-title":"Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development","volume":"89","author":"Otto","year":"1997","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/ng0195-15","article-title":"The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos","volume":"9","author":"Wright","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/8792","article-title":"Sox9 is required for cartilage formation","volume":"22","author":"Bi","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/372525a0","article-title":"Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene","volume":"372","author":"Foster","year":"1994","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0092-8674(94)90041-8","article-title":"Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9","volume":"79","author":"Wagner","year":"1994","journal-title":"Cell"},{"key":"ref_18","first-page":"1028","article-title":"Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal","volume":"57","author":"Kwok","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/BF02265263","article-title":"Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9","volume":"97","author":"Wirth","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00774-005-0610-y","article-title":"Distinct roles of Sox5, Sox6, and Sox9 in different stages of chondrogenic differentiation","volume":"23","author":"Ikeda","year":"2005","journal-title":"J. Bone Miner. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14665","DOI":"10.1073\/pnas.0504750102","article-title":"Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors","volume":"102","author":"Akiyama","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19004","DOI":"10.1073\/pnas.0605170103","article-title":"Dominance of SOX9 function over RUNX2 during skeletogenesis","volume":"103","author":"Zhou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1074\/jbc.M808048200","article-title":"Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus","volume":"284","author":"Topol","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.devcel.2011.12.024","article-title":"Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes","volume":"22","author":"Dy","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1242\/dev.043281","article-title":"Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription","volume":"136","author":"Wang","year":"2009","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e37673","DOI":"10.7554\/eLife.37673","article-title":"Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia","volume":"7","author":"Wang","year":"2018","journal-title":"eLife"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1083\/jcb.200211089","article-title":"Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo","volume":"162","author":"Zheng","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.136.2.459","article-title":"Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: Implications for function","volume":"136","author":"Kwan","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S1534-5807(02)00157-0","article-title":"Reaching a genetic and molecular understanding of skeletal development","volume":"2","author":"Karsenty","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1242\/dev.126.6.1149","article-title":"VEGF is required for growth and survival in neonatal mice","volume":"126","author":"Gerber","year":"1999","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"a008334","DOI":"10.1101\/cshperspect.a008334","article-title":"Development of the endochondral skeleton","volume":"5","author":"Long","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of bone development and repair","volume":"21","author":"Salhotra","year":"2020","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/ncb3067","article-title":"A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones","volume":"16","author":"Ono","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/cr.2014.111","article-title":"Osteogenic fate of hypertrophic chondrocytes","volume":"24","author":"Yang","year":"2014","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12097","DOI":"10.1073\/pnas.1302703111","article-title":"Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1242\/bio.201411031","article-title":"Dual pathways to endochondral osteoblasts: A novel chondrocyte-derived osteoprogenitor cell identified in hypertrophic cartilage","volume":"4","author":"Park","year":"2015","journal-title":"Biol. Open"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/dgd.12203","article-title":"Fate of growth plate hypertrophic chondrocytes: Death or lineage extension?","volume":"57","author":"Tsang","year":"2015","journal-title":"Dev. Growth Differ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41586-018-0662-5","article-title":"Resting zone of the growth plate houses a unique class of skeletal stem cells","volume":"563","author":"Mizuhashi","year":"2018","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhou, X., von der Mark, K., Henry, S., Norton, W., Adams, H., and de Crombrugghe, B. (2014). Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004820"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1002\/jbmr.4132","article-title":"IRX3 and IRX5 Inhibit Adipogenic Differentiation of Hypertrophic Chondrocytes and Promote Osteogenesis","volume":"35","author":"Tan","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1002\/jcp.24045","article-title":"Targeting Runx2 expression in hypertrophic chondrocytes impairs endochondral ossification during early skeletal development","volume":"227","author":"Ding","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1242\/dev.102210","article-title":"Skeletal stem cells","volume":"142","author":"Bianco","year":"2015","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the Human Skeletal Stem Cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1038\/s41467-019-11100-4","article-title":"Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life","volume":"10","author":"Pineault","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.cell.2014.11.042","article-title":"Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential","volume":"160","author":"Worthley","year":"2015","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/stem.3318","article-title":"Telomerase expression marks transitional growth-associated skeletal progenitor\/stem cells","volume":"39","author":"Carlone","year":"2021","journal-title":"Stem Cells"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Allen, M.R., and Burr, D.B. (2019). Bone Growth, Modeling, and Remodeling. Basic and Applied Bone Biology, Elsevier, Inc.. [2nd ed.].","DOI":"10.1016\/B978-0-12-813259-3.00005-1"},{"key":"ref_48","unstructured":"Burr, D., and Allen, M.R. (2019). Skeletal Changes Across the Life Span. Basic and Applied Bone Biology, Elsevier, Inc.. [2nd ed.]."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.devcel.2005.03.016","article-title":"Wnt\/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis","volume":"8","author":"Day","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.devcel.2005.02.013","article-title":"Canonical Wnt\/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes","volume":"8","author":"Hill","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1002\/jbmr.1694","article-title":"Loss of wnt\/beta-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes","volume":"27","author":"Song","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1242\/dev.137489","article-title":"beta-catenin activity in late hypertrophic chondrocytes locally orchestrates osteoblastogenesis and osteoclastogenesis","volume":"143","author":"Houben","year":"2016","journal-title":"Development"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.2106\/JBJS.M.01096","article-title":"A review of osteocyte function and the emerging importance of sclerostin","volume":"96","author":"Compton","year":"2014","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20031454","article-title":"Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist","volume":"199","author":"Roelen","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nature01657","article-title":"Developmental regulation of the growth plate","volume":"423","author":"Kronenberg","year":"2003","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/ng0797-307","article-title":"Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2\/CBFA1 in cleidocranial dysplasia","volume":"16","author":"Lee","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1101\/gad.1174704","article-title":"Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog","volume":"18","author":"Yoshida","year":"2004","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Komori, T. (2010). Signaling networks in RUNX2-dependent bone development. J. Cell. Biochem.","DOI":"10.1002\/jcb.22994"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1128\/MCB.15.4.1858","article-title":"Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene","volume":"15","author":"Ducy","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0092-8674(00)80257-3","article-title":"Osf2\/Cbfa1: A transcriptional activator of osteoblast differentiation","volume":"89","author":"Ducy","year":"1997","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/ng1015","article-title":"Core-binding factor beta interacts with Runx2 and is required for skeletal development","volume":"32","author":"Yoshida","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00441-009-0832-8","article-title":"Regulation of bone development and extracellular matrix protein genes by RUNX2","volume":"339","author":"Komori","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16016","DOI":"10.1074\/jbc.M114.552216","article-title":"The RUNX2 cistrome in osteoblasts: Characterization, down-regulation following differentiation, and relationship to gene expression","volume":"289","author":"Meyer","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R52","DOI":"10.1186\/gb-2014-15-3-r52","article-title":"Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis","volume":"15","author":"Wu","year":"2014","journal-title":"Genome Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1083\/jcb.200105052","article-title":"Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures","volume":"155","author":"Liu","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000151719","article-title":"Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2-SMAD complex to promote osteoblast differentiation","volume":"189","author":"Javed","year":"2009","journal-title":"Cells Tissues Organs."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/j.celrep.2016.02.021","article-title":"Yap1 Regulates Multiple Steps of Chondrocyte Differentiation during Skeletal Development and Bone Repair","volume":"14","author":"Deng","year":"2016","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbrc.2007.12.100","article-title":"Hes1 stimulates transcriptional activity of Runx2 by increasing protein stabilization during osteoblast differentiation","volume":"367","author":"Suh","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1242\/dev.029355","article-title":"Hand2 controls osteoblast differentiation in the branchial arch by inhibiting DNA binding of Runx2","volume":"136","author":"Funato","year":"2009","journal-title":"Development"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.cell.2015.05.029","article-title":"Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation","volume":"161","author":"Wei","year":"2015","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1534-5807(04)00058-9","article-title":"A twist code determines the onset of osteoblast differentiation","volume":"6","author":"Bialek","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9248","DOI":"10.1128\/MCB.24.20.9248-9261.2004","article-title":"Dlx3 transcriptional regulation of osteoblast differentiation: Temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene","volume":"24","author":"Hassan","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/74231","article-title":"Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation","volume":"24","author":"Satokata","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1089\/ten.tea.2010.0503","article-title":"Roles of SATB2 in osteogenic differentiation and bone regeneration","volume":"17","author":"Zhang","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0092-8674(01)00622-5","article-title":"The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation","volume":"108","author":"Nakashima","year":"2002","journal-title":"Cell"},{"key":"ref_76","first-page":"126","article-title":"Transcriptional regulation of bone formation","volume":"3","author":"Baek","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1359\/jbmr.081248","article-title":"Positive regulation of adult bone formation by osteoblast-specific transcription factor osterix","volume":"24","author":"Baek","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12919","DOI":"10.1073\/pnas.0912855107","article-title":"Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice","volume":"107","author":"Zhou","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1101\/gad.13.8.1025","article-title":"A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development","volume":"13","author":"Ducy","year":"1999","journal-title":"Genes Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.bbrc.2003.08.058","article-title":"BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2","volume":"309","author":"Lee","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm1270","article-title":"NFAT and Osterix cooperatively regulate bone formation","volume":"11","author":"Koga","year":"2005","journal-title":"Nat. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.1073\/pnas.0710831105","article-title":"Inhibition of Wnt signaling by the osteoblast-specific transcription factor Osterix","volume":"105","author":"Zhang","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bone.2011.05.023","article-title":"Unraveling the role of FoxOs in bone\u2014Insights from mouse models","volume":"49","author":"Almeida","year":"2011","journal-title":"Bone"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"31055","DOI":"10.1074\/jbc.M109.079962","article-title":"Foxo1, a novel regulator of osteoblast differentiation and skeletogenesis","volume":"285","author":"Teixeira","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e12540","DOI":"10.1111\/cpr.12540","article-title":"Bidirectional regulation of osteogenic differentiation by the FOXO subfamily of Forkhead transcription factors in mammalian MSCs","volume":"52","author":"Chen","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cmet.2010.01.001","article-title":"FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts","volume":"11","author":"Rached","year":"2010","journal-title":"Cell Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2014.01.021","article-title":"The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness","volume":"62","author":"Makowski","year":"2014","journal-title":"Bone"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cell.2006.05.012","article-title":"SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation","volume":"125","author":"Dobreva","year":"2006","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0092-8674(04)00344-7","article-title":"ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: Implication for Coffin-Lowry Syndrome","volume":"117","author":"Yang","year":"2004","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Yu, S., Franceschi, R.T., Luo, M., Fan, J., Jiang, D., Cao, H., Kwon, T.G., Lai, Y., Zhang, J., and Patrene, K. (2009). Critical role of activating transcription factor 4 in the anabolic actions of parathyroid hormone in bone. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007583"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.cmet.2006.10.010","article-title":"ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae","volume":"4","author":"Elefteriou","year":"2006","journal-title":"Cell Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/dbio.2002.0817","article-title":"The Fused toes (Ft) mouse mutation causes anteroposterior and dorsoventral polydactyly","volume":"251","author":"Grotewold","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s00335-001-2142-7","article-title":"The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster","volume":"13","author":"Peters","year":"2002","journal-title":"Mamm. Genome"},{"key":"ref_94","first-page":"1015","article-title":"Consanguinity and genetic disorders. Profile from Jordan","volume":"28","author":"Hamamy","year":"2007","journal-title":"Saudi Med. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/ajmg.a.31594","article-title":"Severe hypertelorism, midface prominence, prominent\/simple ears, severe myopia, borderline intelligence, and bone fragility in two brothers: New syndrome?","volume":"143","author":"Hamamy","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/ng.2259","article-title":"Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1","volume":"44","author":"Bonnard","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1002\/ajmg.a.33580","article-title":"Identification of a submicroscopic 3.2 Mb chromosomal 16q12.2-13 deletion in a child with short stature, mild developmental delay, and craniofacial anomalies, by high-density oligonucleotide array\u2014A recognizable syndrome","volume":"152","author":"Chang","year":"2010","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1242\/dev.081703","article-title":"Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology","volume":"139","author":"Gaborit","year":"2012","journal-title":"Development"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.devcel.2014.03.001","article-title":"Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling","volume":"29","author":"Li","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bonr.2016.02.005","article-title":"Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization","volume":"5","author":"Cain","year":"2016","journal-title":"Bone Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1023\/A:1011513223894","article-title":"Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis","volume":"2","author":"Justesen","year":"2001","journal-title":"Biogerontology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/jcp.25406","article-title":"Runx2\/DICER\/miRNA Pathway in Regulating Osteogenesis","volume":"232","author":"Zheng","year":"2017","journal-title":"J. Cell Physiol."},{"key":"ref_103","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_104","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ydbio.2010.01.008","article-title":"Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse","volume":"340","author":"Gaur","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"115760","DOI":"10.1016\/j.bone.2020.115760","article-title":"The role of microRNAs in bone development","volume":"143","author":"Hensley","year":"2021","journal-title":"Bone"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1016\/j.febslet.2015.09.032","article-title":"MiR-455-3p regulates early chondrogenic differentiation via inhibiting Runx2","volume":"589","author":"Zhang","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.biochi.2018.12.006","article-title":"Parathyroid hormone-stimulation of Runx2 during osteoblast differentiation via the regulation of lnc-SUPT3H-1:16 (RUNX2-AS1:32) and miR-6797-5p","volume":"158","author":"Arumugam","year":"2019","journal-title":"Biochimie"},{"key":"ref_109","first-page":"3379","article-title":"MicroRNA-155 inhibits the osteogenic differentiation of mesenchymal stem cells induced by BMP9 via downregulation of BMP signaling pathway","volume":"41","author":"Liu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/bdrc.20043","article-title":"Runx2: A master organizer of gene transcription in developing and maturing osteoblasts","volume":"75","author":"Schroeder","year":"2005","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1159\/000457013","article-title":"MiR-125b Regulates the Osteogenic Differentiation of Human Mesenchymal Stem Cells by Targeting BMPR1b","volume":"41","author":"Wang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_112","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_113","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.febslet.2012.05.049","article-title":"MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2","volume":"586","author":"Zeng","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/dbio.1998.9197","article-title":"A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction","volume":"208","author":"Miyama","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1128\/MCB.01544-06","article-title":"HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes","volume":"27","author":"Hassan","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000438607","article-title":"MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting HOXA10","volume":"38","author":"Huang","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"19272","DOI":"10.1074\/jbc.M109.014001","article-title":"MicroRNA-141 and -200a are involved in bone morphogenetic protein-2-induced mouse pre-osteoblast differentiation by targeting distal-less homeobox 5","volume":"284","author":"Itoh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/jcb.20805","article-title":"Transcriptional co-repressors of Runx2","volume":"98","author":"Westendorf","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"12328","DOI":"10.1074\/jbc.M110.176099","article-title":"A Runx2\/miR-3960\/miR-2861 regulatory feedback loop during mouse osteoblast differentiation","volume":"286","author":"Hu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"15676","DOI":"10.1074\/jbc.M809787200","article-title":"Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/03008207.2019.1643334","article-title":"MicroRNA-145 suppresses osteogenic differentiation of human jaw bone marrow mesenchymal stem cells partially via targeting semaphorin 3A","volume":"61","author":"Jin","year":"2020","journal-title":"Connect. Tissue Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/j.febslet.2013.07.030","article-title":"miR-145 suppresses osteogenic differentiation by targeting Sp7","volume":"587","author":"Jia","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1007\/s00018-019-03162-w","article-title":"Deregulated miRNAs in osteoporosis: Effects in bone metastasis","volume":"76","author":"Bellavia","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Bottani, M., Banfi, G., and Lombardi, G. (2020). The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases. Biomolecules, 10.","DOI":"10.3390\/biom10040589"},{"key":"ref_125","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_126","doi-asserted-by":"crossref","first-page":"115787","DOI":"10.1016\/j.bone.2020.115787","article-title":"Circulating miRNAs in bone health and disease","volume":"145","author":"Grillari","year":"2021","journal-title":"Bone"},{"key":"ref_127","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_128","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/emmm.201201606","article-title":"SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating \u03b2-catenin","volume":"5","author":"Simic","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1186\/s13287-020-01966-3","article-title":"Epidrugs: Novel epigenetic regulators that open a new window for targeting osteoblast differentiation","volume":"11","author":"Ghorbaninejad","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"25283","DOI":"10.1038\/srep25283","article-title":"Inhibiting DNA methylation switches adipogenesis to osteoblastogenesis by activating Wnt10a","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_131","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_132","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/jcb.20544","article-title":"Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors","volume":"96","author":"Cho","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.bbrc.2007.02.057","article-title":"Sodium butyrate activates ERK to regulate differentiation of mesenchymal stem cells","volume":"355","author":"Chen","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/dgd.12119","article-title":"Histone deacetylase inhibitor sodium butyrate promotes the osteogenic differentiation of rat adipose-derived stem cells","volume":"56","author":"Hu","year":"2014","journal-title":"Dev. Growth Differ."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.coph.2015.03.005","article-title":"Parathyroid hormone: Anabolic and catabolic actions on the skeleton","volume":"22","author":"Silva","year":"2015","journal-title":"Curr. Opin. Pharm."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1002\/jbmr.5650111003","article-title":"Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages","volume":"11","author":"Isogai","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"50259","DOI":"10.1074\/jbc.M307444200","article-title":"Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism","volume":"278","author":"Bellido","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"36659","DOI":"10.1074\/jbc.M109.016915","article-title":"Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts","volume":"284","author":"Nagase","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Kawai, Y., Komori, H., Rokutanda, S., Eguchi, Y., Tsujimoto, Y., Asahina, I., and Komori, T. (2014). Bcl2 deficiency activates FoxO through Akt inactivation and accelerates osteoblast differentiation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086629"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1083\/jcb.200507106","article-title":"p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling","volume":"172","author":"Wang","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Komori, T. (2016). Cell Death in Chondrocytes, Osteoblasts, and Osteocytes. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122045"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41413-020-0099-y","article-title":"Molecular mechanosensors in osteocytes","volume":"8","author":"Qin","year":"2020","journal-title":"Bone Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Guasto, A., and Cormier-Daire, V. (2021). Signaling Pathways in Bone Development and Their Related Skeletal Dysplasia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094321"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3389\/fcell.2020.00781","article-title":"Extracellular Matrix and Cellular Plasticity in Musculoskeletal Development","volume":"8","author":"Ma","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Amarasekara, D.S., Kim, S., and Rho, J. (2021). Regulation of Osteoblast Differentiation by Cytokine Networks. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062851"},{"key":"ref_146","first-page":"99","article-title":"Effect of stilbestrol in post-menopausal osteoporosis","volume":"14","author":"Albright","year":"1946","journal-title":"Trans. Conf. Metab. Asp. Conval"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1093\/nar\/29.14.2905","article-title":"Estrogen receptor interaction with estrogen response elements","volume":"29","author":"Klinge","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1210\/me.2010-0463","article-title":"GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription","volume":"25","author":"Guemes","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/jbm4.10027","article-title":"GATA4 Directly Regulates","volume":"2","author":"Khalid","year":"2018","journal-title":"JBMR Plus"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.286.5440.768","article-title":"Light-independent role of CRY1 and CRY2 in the mammalian circadian clock","volume":"286","author":"Griffin","year":"1999","journal-title":"Science"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1126\/science.288.5468.1013","article-title":"Interacting molecular loops in the mammalian circadian clock","volume":"288","author":"Shearman","year":"2000","journal-title":"Science"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-neuro-060909-153128","article-title":"Central and peripheral circadian clocks in mammals","volume":"35","author":"Mohawk","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2013.05.012","article-title":"The circadian clock and glucocorticoids--interactions across many time scales","volume":"380","author":"Dickmeis","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, C.F., and Meng, Q.J. (2019). Timing metabolism in cartilage and bone: Links between circadian clocks and tissue homeostasis. J. Endocrinol.","DOI":"10.1530\/JOE-19-0256"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1126\/science.280.5369.1564","article-title":"Role of the CLOCK protein in the mammalian circadian mechanism","volume":"280","author":"Gekakis","year":"1998","journal-title":"Science"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0092-8674(00)81014-4","article-title":"mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop","volume":"98","author":"Kume","year":"1999","journal-title":"Cell"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S0092-8674(01)00610-9","article-title":"Posttranslational mechanisms regulate the mammalian circadian clock","volume":"107","author":"Lee","year":"2001","journal-title":"Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2106","article-title":"Post-translational modifications regulate the ticking of the circadian clock","volume":"8","author":"Gallego","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/B978-0-12-387690-4.00006-4","article-title":"Genetics of circadian rhythms in Mammalian model organisms","volume":"74","author":"Lowrey","year":"2011","journal-title":"Adv. Genet."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00774-013-0428-y","article-title":"PCAF acetylates Runx2 and promotes osteoblast differentiation","volume":"31","author":"Wang","year":"2013","journal-title":"J. Bone Miner. Metab."},{"key":"ref_161","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_162","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00198-008-0729-5","article-title":"Nightshift work and fracture risk: The Nurses\u2019 Health Study","volume":"20","author":"Feskanich","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"9156478","DOI":"10.1155\/2018\/9156478","article-title":"Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?","volume":"2018","author":"Song","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Gnocchi, D., and Bruscalupi, G. (2017). Circadian Rhythms and Hormonal Homeostasis: Pathophysiological Implications. Biology, 6.","DOI":"10.3390\/biology6010010"},{"key":"ref_165","first-page":"281","article-title":"The parathyroid hormone circadian rhythm is truly endogenous\u2014A general clinical research center study","volume":"82","author":"Klerman","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.cell.2005.06.028","article-title":"The molecular clock mediates leptin-regulated bone formation","volume":"122","author":"Fu","year":"2005","journal-title":"Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jcb.22957","article-title":"Per-1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH","volume":"112","author":"Hanyu","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3109\/17453674.2015.1029393","article-title":"Parathyroid hormone resets the cartilage circadian clock of the organ-cultured murine femur","volume":"86","author":"Okubo","year":"2015","journal-title":"Acta Orthop."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1359\/jbmr.061114","article-title":"Circadian oscillation of gene expression in murine calvarial bone","volume":"22","author":"Zvonic","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Okubo, N., Minami, Y., Fujiwara, H., Umemura, Y., Tsuchiya, Y., Shirai, T., Oda, R., Inokawa, H., Kubo, T., and Yagita, K. (2013). Prolonged bioluminescence monitoring in mouse ex vivo bone culture revealed persistent circadian rhythms in articular cartilages and growth plates. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078306"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"22409","DOI":"10.1038\/srep22409","article-title":"A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site","volume":"6","author":"Kunimoto","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1177\/0022034508328012","article-title":"Circadian rhythm of osteocalcin in the maxillomandibular complex","volume":"88","author":"Gafni","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Wang, Y., Nizkorodov, A., Riemenschneider, K., Lee, C.S., Olivares-Navarrete, R., Schwartz, Z., and Boyan, B.D. (2014). Impaired bone formation in Pdia3 deficient mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112708"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/jbmr.3046","article-title":"The Circadian Gene Clock Regulates Bone Formation Via PDIA3","volume":"32","author":"Yuan","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.bone.2016.01.006","article-title":"Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype","volume":"84","author":"Samsa","year":"2016","journal-title":"Bone"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"111163","DOI":"10.1016\/j.exger.2020.111163","article-title":"A matter of time: Circadian clocks in osteoarthritis and the potential of chronotherapy","volume":"143","author":"Dernie","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/nature06394","article-title":"CLOCK-mediated acetylation of BMAL1 controls circadian function","volume":"450","author":"Hirayama","year":"2007","journal-title":"Nature"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cell.2008.07.002","article-title":"The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control","volume":"134","author":"Nakahata","year":"2008","journal-title":"Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2008.06.050","article-title":"SIRT1 regulates circadian clock gene expression through PER2 deacetylation","volume":"134","author":"Asher","year":"2008","journal-title":"Cell"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Shakibaei, M., Shayan, P., Busch, F., Aldinger, C., Buhrmann, C., Lueders, C., and Mobasheri, A. (2012). Resveratrol mediated modulation of Sirt-1\/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: Potential role of Runx2 deacetylation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035712"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Zainabadi, K., Liu, C.J., and Guarente, L. (2017). SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178520"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.cell.2021.03.010","article-title":"Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption","volume":"184","author":"McDonald","year":"2021","journal-title":"Cell"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.abb.2008.03.027","article-title":"Osteoclast-osteoblast communication","volume":"473","author":"Matsuo","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar2165","article-title":"Biology of RANK, RANKL, and osteoprotegerin","volume":"9 (Suppl. S1)","author":"Boyce","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Kim, J.M., Lin, C., Stavre, Z., Greenblatt, M.B., and Shim, J.H. (2020). Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells, 9.","DOI":"10.3390\/cells9092073"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nm.1979","article-title":"TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation","volume":"15","author":"Tang","year":"2009","journal-title":"Nat. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/nm.2793","article-title":"Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells","volume":"18","author":"Xian","year":"2012","journal-title":"Nat. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.cmet.2007.05.001","article-title":"Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction","volume":"5","author":"Tatsumi","year":"2007","journal-title":"Cell Metab."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/s41467-019-08778-x","article-title":"TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone","volume":"10","author":"Saito","year":"2019","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:05:37Z","timestamp":1760162737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":190,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22115445"],"URL":"https:\/\/doi.org\/10.3390\/ijms22115445","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]}}}