{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:49:22Z","timestamp":1790095762318,"version":"4.0.1"},"reference-count":147,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japanese Ministry of Education, Culture, Sports, Science and Technology","award":["23H00440"],"award-info":[{"award-number":["23H00440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The cotranscription factor Cbfb (core binding factor beta), which enhances the DNA-binding capacity of Runx2 and stabilizes the Runx2 protein, is necessary for bone development. Runx2 is essential for chondrocyte maturation, and Sp7 is partly involved. Runx2 induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances the proliferation of osteoprogenitors. Reciprocal regulation between Runx2 and the Hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathways and Dlx5 (distal-less homeobox 5) plays an important role in these processes. The induction of Fgfr2 (Fgf receptor 2) and Fgfr3 expression by Runx2 is important for the proliferation of osteoblast lineage cells. Runx2 induces Sp7 expression, and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Sp7 induces the differentiation of preosteoblasts into osteoblasts without enhancing their proliferation. In osteoblasts, Runx2 is required for bone formation by inducing the expression of major bone matrix protein genes, including Col1a1 (collagen type I alpha 1), Col1a2, Spp1 (secreted phosphoprotein 1), Ibsp (integrin binding sialoprotein), and Bglap (bone gamma carboxyglutamate protein)\/Bglap2. Bglap\/Bglap2 (osteocalcin) regulates the alignment of apatite crystals parallel to collagen fibrils but does not function as a hormone that regulates glucose metabolism, testosterone synthesis, and muscle mass. Sp7 is also involved in Co1a1 expression and regulates osteoblast\/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.<\/jats:p>","DOI":"10.3390\/ijms251810102","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T02:47:07Z","timestamp":1726800427000},"page":"10102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Regulation of Skeletal Development and Maintenance by Runx2 and Sp7"],"prefix":"10.3390","volume":"25","author":[{"given":"Toshihisa","family":"Komori","sequence":"first","affiliation":[{"name":"Department of Molecular Tumor Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0092-8674(00)80258-5","article-title":"Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts","volume":"89","author":"Komori","year":"1997","journal-title":"Cell"},{"key":"ref_2","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_3","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_4","doi-asserted-by":"crossref","unstructured":"Komori, T. (2022). Whole Aspect of Runx2 Functions in Skeletal Development. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105776"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11669","DOI":"10.1074\/jbc.RA119.007896","article-title":"Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation","volume":"295","author":"Tang","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1042\/BCJ20200036","article-title":"Runx1 up-regulates chondrocyte to osteoblast lineage commitment and promotes bone formation by enhancing both chondrogenesis and osteogenesis","volume":"477","author":"Tang","year":"2020","journal-title":"Biochem. J."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1128\/MCB.01106-14","article-title":"Loss of osteoblast Runx3 produces severe congenital osteopenia","volume":"35","author":"Bauer","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1002\/jbmr.2240","article-title":"Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression","volume":"29","author":"Kawane","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.devcel.2016.04.002","article-title":"Sp7\/Osterix Is Restricted to Bone-Forming Vertebrates where It Acts as a Dlx Co-factor in Osteoblast Specification","volume":"37","author":"Hojo","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33179","DOI":"10.1074\/jbc.M111.337063","article-title":"Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase 13 (MMP13) expression in association with transcription factor Runx2 during endochondral ossification","volume":"287","author":"Nishimura","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yoshida, C.A., Komori, H., Maruyama, Z., Miyazaki, T., Kawasaki, K., Furuichi, T., Fukuyama, R., Mori, M., Yamana, K., and Nakamura, K. (2012). SP7 Inhibits Osteoblast Differentiation at a Late Stage in Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032364"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111315","DOI":"10.1016\/j.celrep.2022.111315","article-title":"Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages","volume":"40","author":"Hojo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42386","DOI":"10.7554\/eLife.42386","article-title":"Reactivation of a developmental Bmp2 signaling center is required for therapeutic control of the murine periosteal niche","volume":"8","author":"Salazar","year":"2019","journal-title":"Elife"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Qin, X., Jiang, Q., Nagano, K., Moriishi, T., Miyazaki, T., Komori, H., Ito, K., Mark, K.V., Sakane, C., and Kaneko, H. (2020). Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1009169"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jot.2024.06.005","article-title":"Roles of Sp7 in osteoblasts for the proliferation, differentiation, and osteocyte process formation","volume":"47","author":"Jiang","year":"2024","journal-title":"J. Orthop. Translat"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0925-4773(98)00210-X","article-title":"Regulation of chondrocyte differentiation by Cbfa1","volume":"80","author":"Kim","year":"1999","journal-title":"Mech. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<279::AID-AJA1>3.0.CO;2-W","article-title":"Maturational disturbance of chondrocytes in Cbfa1-deficient mice","volume":"214","author":"Inada","year":"1999","journal-title":"Dev. Dyn."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"8695","DOI":"10.1074\/jbc.275.12.8695","article-title":"Cbfa1 is a positive regulatory factor in chondrocyte maturation","volume":"275","author":"Enomoto","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1083\/jcb.153.1.87","article-title":"Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes","volume":"153","author":"Ueta","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1101\/gad.845101","article-title":"Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice","volume":"15","author":"Takeda","year":"2001","journal-title":"Genes. Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1002\/jbmr.1945","article-title":"An analysis of skeletal development in osteoblast-specific and chondrocyte-specific runt-related transcription factor-2 (Runx2) knockout mice","volume":"28","author":"Takarada","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1002\/jbmr.2287","article-title":"Runx2 regulates endochondral ossification through control of chondrocyte proliferation and differentiation","volume":"29","author":"Chen","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1126\/science.273.5275.613","article-title":"Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein","volume":"273","author":"Vortkamp","year":"1996","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1053\/joca.2002.0860","article-title":"Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP)","volume":"11","author":"Iwamoto","year":"2003","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.yexcr.2004.05.025","article-title":"Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway","volume":"299","author":"Li","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ydbio.2005.12.044","article-title":"PTH\/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways","volume":"292","author":"Guo","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0925-4773(01)00428-2","article-title":"Tissue specific regulation of VEGF expression during bone development requires Cbfa1\/Runx2","volume":"106","author":"Zelzer","year":"2001","journal-title":"Mech. Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1359\/jbmr.2002.17.7.1297","article-title":"Impaired vascular invasion of Cbfa1-deficient cartilage engrafted in the spleen","volume":"17","author":"Himeno","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1242\/dev.01053","article-title":"VEGFA is necessary for chondrocyte survival during bone development","volume":"131","author":"Zelzer","year":"2004","journal-title":"Development"},{"key":"ref_33","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_34","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_35","doi-asserted-by":"crossref","unstructured":"Kawane, T., Qin, X., Jiang, Q., Miyazaki, T., Komori, H., Yoshida, C.A., Matsuura-Kawata, V., Sakane, C., Matsuo, Y., and Nagai, K. (2018). Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31853-0"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1101\/gad.13.16.2072","article-title":"Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation","volume":"13","author":"Hammerschmidt","year":"1999","journal-title":"Genes. Dev."},{"key":"ref_37","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_38","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_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1242\/dev.01564","article-title":"Sequential roles of Hedgehog and Wnt signaling in osteoblast development","volume":"132","author":"Hu","year":"2005","journal-title":"Development"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1242\/dev.02480","article-title":"Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors","volume":"133","author":"Rodda","year":"2006","journal-title":"Development"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1093\/hmg\/ddy386","article-title":"Runx2 regulates cranial suture closure by inducing hedgehog, Fgf, Wnt and Pthlh signaling pathway gene expressions in suture mesenchymal cells","volume":"28","author":"Qin","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.bone.2009.12.007","article-title":"Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance","volume":"46","author":"Baek","year":"2010","journal-title":"Bone"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ydbio.2016.03.011","article-title":"Osterix\/Sp7 limits cranial bone initiation sites and is required for formation of sutures","volume":"413","author":"Kague","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3109\/03008207.2014.923873","article-title":"Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis","volume":"55","author":"Adhami","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1002\/jbmr.4386","article-title":"Runt-related transcription factor-2 (Runx2) is required for bone matrix protein gene expression in committed osteoblasts in mice","volume":"36","author":"Qin","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jiang, Q., Qin, X., Moriishi, T., Fukuyama, R., Katsumata, S., Matsuzaki, H., Komori, H., Matsuo, Y., Sakane, C., and Ito, K. (2024). Runx2 Regulates Galnt3 and Fgf23 Expressions and Galnt3 Decelerates Osteoid Mineralization by Stabilizing Fgf23. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042275"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00774-019-01066-0","article-title":"How do we sense phosphate to regulate serum phosphate level?","volume":"38","author":"Fukumoto","year":"2020","journal-title":"J. Bone Miner. Metab."},{"key":"ref_49","first-page":"1","article-title":"Osterix regulates corticalization for longitudinal bone growth via integrin \u03b23 expression","volume":"50","author":"Moon","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.2106\/00004623-200309000-00013","article-title":"Mechanisms responsible for longitudinal growth of the cortex: Coalescence of trabecular bone into cortical bone","volume":"85","author":"Cadet","year":"2003","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0022-4731(89)90092-7","article-title":"Evidence for a direct effect of estrogen on bone cells in vitro","volume":"34","author":"Ernst","year":"1989","journal-title":"J. Steroid Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0006-291X(05)80774-0","article-title":"Stimulatory effects of estrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro","volume":"186","author":"Scheven","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","first-page":"381","article-title":"Regulatory effect of estrogen receptor-\u03b1-mediated Wnt\/\u03b2-catenin signaling pathway on osteoblast proliferation","volume":"30","author":"Han","year":"2016","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chuang, S.C., Chen, C.H., Chou, Y.S., Ho, M.L., and Chang, J.K. (2020). G Protein-Coupled Estrogen Receptor Mediates Cell Proliferation through the cAMP\/PKA\/CREB Pathway in Murine Bone Marrow Mesenchymal Stem Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186490"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"124","DOI":"10.14715\/cmb\/2022.68.1.16","article-title":"Effects of Estrogen on Proliferation and Apoptosis of Osteoblasts through Regulating GPER\/AKT Pathway","volume":"68","author":"Zhang","year":"2022","journal-title":"Cell Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/s41586-023-06519-1","article-title":"A vertebral skeletal stem cell lineage driving metastasis","volume":"621","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Moriishi, T., and Komori, T. (2022). Osteocytes: Their Lacunocanalicular Structure and Mechanoresponses. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084373"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6271","DOI":"10.1038\/s41467-021-26571-7","article-title":"Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"50563","DOI":"10.1074\/jbc.M307310200","article-title":"Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype","volume":"278","author":"Thomas","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109380","DOI":"10.1016\/j.celrep.2021.109380","article-title":"Mechanical load regulates bone growth via periosteal Osteocrin","volume":"36","author":"Ochi","year":"2021","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s10735-016-9686-z","article-title":"Maturation of cortical bone suppresses periosteal osteoprogenitor proliferation in a paracrine manner","volume":"47","author":"Moon","year":"2016","journal-title":"J. Mol. Histol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.1074\/jbc.M705092200","article-title":"Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost\/sclerostin","volume":"283","author":"Robling","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1359\/jbmr.090411","article-title":"Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt\/beta-catenin signaling","volume":"24","author":"Lin","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00198-011-1656-4","article-title":"Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered","volume":"23","author":"Moustafa","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Fukuyama, R., Ito, M., Miyazaki, T., Maeno, T., Kawai, Y., Komori, H., and Komori, T. (2012). Osteocyte network; a negative regulatory system for bone mass augmented by the induction of rankl in osteoblasts and sost in osteocytes at unloading. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040143"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Ito, T., Fukuyama, R., Qin, X., Komori, H., Kaneko, H., Matsuo, Y., Yoshida, N., and Komori, T. (2022). Sp7 Transgenic Mice with a Markedly Impaired Lacunocanalicular Network Induced Sost and Reduced Bone Mass by Unloading. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063173"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/382448a0","article-title":"Increased bone formation in osteocalcin-deficient mice","volume":"382","author":"Ducy","year":"1996","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/nyas.13470","article-title":"Osteocalcin and osteopontin influence bone morphology and mechanical properties","volume":"1409","author":"Bailey","year":"2017","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1146\/annurev-nutr-061121-091348","article-title":"Osteocalcin: A Multifaceted Bone-Derived Hormone","volume":"43","author":"Karsenty","year":"2023","journal-title":"Annu. Rev. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Diegel, C.R., Hann, S., Ayturk, U.M., Hu, J.C.W., Lim, K.E., Droscha, C.J., Madaj, Z.B., Foxa, G.E., Izaguirre, I., and Transgenics Core, V.V.A. (2020). An osteocalcin-deficient mouse strain without endocrine abnormalities. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008361"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Ozasa, R., Ishimoto, T., Nakano, T., Hasegawa, T., Miyazaki, T., Liu, W., Fukuyama, R., Wang, Y., and Komori, H. (2020). Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008586"},{"key":"ref_72","first-page":"1169","article-title":"Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR\/Cas9 technology","volume":"9","author":"Lambert","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2007.05.047","article-title":"Endocrine regulation of energy metabolism by the skeleton","volume":"130","author":"Lee","year":"2007","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cell.2010.06.003","article-title":"Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism","volume":"142","author":"Ferron","year":"2010","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1172\/JCI39366","article-title":"The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts","volume":"119","author":"Yoshizawa","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.cell.2011.02.004","article-title":"Endocrine regulation of male fertility by the skeleton","volume":"144","author":"Oury","year":"2011","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1172\/JCI133572","article-title":"Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts","volume":"130","author":"Chowdhury","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1210\/en.2003-1400","article-title":"Glucose homeostasis and tissue transcript content of insulin signaling intermediates in four inbred strains of mice: C57BL\/6, C57BLKS\/6, DBA\/2, and 129X1","volume":"145","author":"Goren","year":"2004","journal-title":"Endocrinology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0092-8674(00)81389-6","article-title":"The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo","volume":"87","author":"Wang","year":"1996","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"12359","DOI":"10.1073\/pnas.93.22.12359","article-title":"Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta","volume":"93","author":"Sasaki","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ng1050","article-title":"Cbfbeta interacts with Runx2 and has a critical role in bone development","volume":"32","author":"Kundu","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/ng1049","article-title":"The core-binding factor beta subunit is required for bone formation and hematopoietic maturation","volume":"32","author":"Miller","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"8482","DOI":"10.1073\/pnas.1310617111","article-title":"Cbfbeta deletion in mice recapitulates cleidocranial dysplasia and reveals multiple functions of Cbfbeta required for skeletal development","volume":"111","author":"Chen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1002\/jbmr.2275","article-title":"Core binding factor beta (Cbf\u03b2) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation","volume":"29","author":"Fei","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bone.2014.04.031","article-title":"Deletion of core-binding factor beta (Cbfbeta) in mesenchymal progenitor cells provides new insights into Cbfbeta\/Runxs complex function in cartilage and bone development","volume":"65","author":"Wu","year":"2014","journal-title":"Bone"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"861","DOI":"10.7150\/ijbs.8521","article-title":"Chondrocyte-specific Knockout of Cbfbeta Reveals the Indispensable Function of Cbfbeta in Chondrocyte Maturation, Growth Plate Development and Trabecular Bone Formation in Mice","volume":"10","author":"Wu","year":"2014","journal-title":"Int. J. Biol. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/jbmr.2397","article-title":"Core binding factor beta of osteoblasts maintains cortical bone mass via stabilization of Runx2 in mice","volume":"30","author":"Lim","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/jbmr.2379","article-title":"Cbfb regulates bone development by stabilizing Runx family proteins","volume":"30","author":"Qin","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/jbmr.2814","article-title":"Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development","volume":"31","author":"Jiang","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Jiang, Q., Qin, X., Nagano, K., Komori, H., Matsuo, Y., Taniuchi, I., Ito, K., and Komori, T. (2022). Different Requirements of CBFB and RUNX2 in Skeletal Development among Calvaria, Limbs, Vertebrae and Ribs. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113299"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0092-8674(00)80260-3","article-title":"Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia","volume":"89","author":"Mundlos","year":"1997","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"23971","DOI":"10.1074\/jbc.M302457200","article-title":"Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-\/- mice by RANKL transgene","volume":"278","author":"Enomoto","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"36181","DOI":"10.1074\/jbc.M206057200","article-title":"Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1\/Runx2","volume":"277","author":"Xiao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1074\/jbc.M109.055053","article-title":"FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization","volume":"285","author":"Park","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"33132","DOI":"10.1074\/jbc.M500608200","article-title":"Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression","volume":"280","author":"Gaur","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"35579","DOI":"10.1074\/jbc.M502267200","article-title":"Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter","volume":"280","author":"Lee","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1210\/me.2002-0225","article-title":"Parathyroid hormone bone anabolic action requires Cbfa1\/Runx2-dependent signaling","volume":"17","author":"Krishnan","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5037","DOI":"10.1074\/jbc.275.7.5037","article-title":"Parathyroid hormone regulation of the rat collagenase-3 promoter by protein kinase A-dependent transactivation of core binding factor alpha1","volume":"275","author":"Selvamurugan","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ajhg.2010.05.016","article-title":"Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta","volume":"87","author":"Lapunzina","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bone.2018.01.031","article-title":"Novel variant in Sp7\/Osx associated with recessive osteogenesis imperfecta with bone fragility and hearing impairment","volume":"110","author":"Fiscaletti","year":"2018","journal-title":"Bone"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"103954","DOI":"10.1016\/j.ejmg.2020.103954","article-title":"Biallelic variants in four genes underlying recessive osteogenesis imperfecta","volume":"63","author":"Hayat","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"116400","DOI":"10.1016\/j.bone.2022.116400","article-title":"Dominant osteogenesis imperfecta with low bone turnover caused by a heterozygous SP7 variant","volume":"160","author":"Ludwig","year":"2022","journal-title":"Bone"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"ziae026","DOI":"10.1093\/jbmrpl\/ziae026","article-title":"A homozygous SP7\/OSX mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies","volume":"8","author":"Jarragh","year":"2024","journal-title":"JBMR Plus"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11914-023-00778-7","article-title":"SP7: From Bone Development to Skeletal Disease","volume":"21","author":"Wang","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e246554","DOI":"10.1136\/bcr-2021-246554","article-title":"Dental phenotype in an adolescent with osteogenesis imperfecta type XII","volume":"15","author":"Tung","year":"2022","journal-title":"BMJ Case Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"115364","DOI":"10.1016\/j.bone.2020.115364","article-title":"Juvenile Paget\u2019s Disease from Heterozygous Mutation of SP7 Encoding Osterix (Specificity Protein 7, Transcription Factor SP7)","volume":"137","author":"Whyte","year":"2020","journal-title":"Bone"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/s41467-022-28318-4","article-title":"A neomorphic variant in SP7 alters sequence specificity and causes a high-turnover bone disorder","volume":"13","author":"Lui","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"116953","DOI":"10.1016\/j.bone.2023.116953","article-title":"Long-term follow-up of severe autosomal recessive SP7-related bone disorder","volume":"179","author":"Gauthier","year":"2024","journal-title":"Bone"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jot.2019.11.008","article-title":"Runx2 plays a central role in Osteoarthritis development","volume":"23","author":"Chen","year":"2020","journal-title":"J. Orthop. Translat"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.joca.2010.11.004","article-title":"Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells","volume":"19","author":"Tetsunaga","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11033-006-9037-3","article-title":"Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter","volume":"34","author":"Thirunavukkarasu","year":"2007","journal-title":"Mol. Biol. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/sj.onc.1202333","article-title":"Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone","volume":"18","author":"Porte","year":"1999","journal-title":"Oncogene"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"20029","DOI":"10.1074\/jbc.M010601200","article-title":"AP-1 and Cbfa\/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2\/AP-1 composite element","volume":"276","author":"Hess","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Takahashi, A., de Andres, M.C., Hashimoto, K., Itoi, E., Otero, M., Goldring, M.B., and Oreffo, R.O.C. (2017). DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-08418-8"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1093\/hmg\/ddr540","article-title":"C\/EBPbeta and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2alpha as the inducer in chondrocytes","volume":"21","author":"Hirata","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1002\/art.34566","article-title":"Chondrocyte-intrinsic Smad3 represses Runx2-inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis","volume":"64","author":"Chen","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0140-6736(12)60681-3","article-title":"Identification of new susceptibility loci for osteoarthritis (arcOGEN): A genome-wide association study","volume":"380","author":"Zeggini","year":"2012","journal-title":"Lancet"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Castano-Betancourt, M.C., Evans, D.S., Ramos, Y.F., Boer, C.G., Metrustry, S., Liu, Y., den Hollander, W., van Rooij, J., Kraus, V.B., and Yau, M.S. (2016). Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006260"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759720X211006959","article-title":"Promising targets for therapy of osteoarthritis: A review on the Wnt and TGF-\u03b2 signalling pathways","volume":"13","author":"Cherifi","year":"2021","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1002\/art.22041","article-title":"Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability","volume":"54","author":"Kamekura","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Liao, L., Zhang, S., Gu, J., Takarada, T., Yoneda, Y., Huang, J., Zhao, L., Oh, C.D., Li, J., and Wang, B. (2017). Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02490-w"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1002\/jbmr.3737","article-title":"Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice","volume":"34","author":"Catheline","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6187","DOI":"10.1038\/s41467-022-33744-5","article-title":"Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development","volume":"13","author":"Nagata","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"102015","DOI":"10.1016\/j.arr.2023.102015","article-title":"The roles of the Hippo-YAP signalling pathway in Cartilage and Osteoarthritis","volume":"90","author":"Sun","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_128","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_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20120769","article-title":"Teaching an old dogma new tricks: Twenty years of Shc adaptor signalling","volume":"447","author":"Wills","year":"2012","journal-title":"Biochem. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.joca.2022.07.001","article-title":"ShcA promotes chondrocyte hypertrophic commitment and osteoarthritis in mice through RunX2 nuclear translocation and YAP1 inactivation","volume":"30","author":"Courtes","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s43587-021-00165-w","article-title":"Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis","volume":"2","author":"Wu","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1359\/JBMR.050516","article-title":"Runx1\/AML1\/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis","volume":"20","author":"Wang","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/jcp.24727","article-title":"Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading","volume":"230","author":"LeBlanc","year":"2015","journal-title":"J. Cell Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1136\/annrheumdis-2012-201745","article-title":"A novel disease-modifying osteoarthritis drug candidate targeting Runx1","volume":"72","author":"Yano","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Aini, H., Itaka, K., Fujisawa, A., Uchida, H., Uchida, S., Fukushima, S., Kataoka, K., Saito, T., Chung, U.I., and Ohba, S. (2016). Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Sci. Rep., 6.","DOI":"10.1038\/srep18743"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Pezzotti, G., Zhu, W., Terai, Y., Marin, E., Boschetto, F., Kawamoto, K., and Itaka, K. (2022). Raman spectroscopic insight into osteoarthritic cartilage regeneration by mRNA therapeutics encoding cartilage-anabolic transcription factor Runx1. Mater. Today Bio, 13.","DOI":"10.1016\/j.mtbio.2022.100210"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Yano, F., Ohba, S., Murahashi, Y., Tanaka, S., Saito, T., and Chung, U.I. (2019). Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43948-3"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41413-021-00173-x","article-title":"Runx1 protects against the pathological progression of osteoarthritis","volume":"9","author":"Zhou","year":"2021","journal-title":"Bone Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41413-022-00231-y","article-title":"Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP, TGF\u03b2, and Wnt signaling in articular cartilage formation and osteoarthritis","volume":"10","author":"Zhang","year":"2022","journal-title":"Bone Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/01478885.2023.2281790","article-title":"Runx1 alleviates osteoarthritis progression in aging mice","volume":"47","author":"Chen","year":"2024","journal-title":"J. Histotechnol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1006\/dbio.2002.0640","article-title":"Role of Runx genes in chondrocyte differentiation","volume":"245","author":"Stricker","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1359\/jbmr.070502","article-title":"Runx3\/AML2\/Cbfa3 regulates early and late chondrocyte differentiation","volume":"22","author":"Dong","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1002\/jcp.24396","article-title":"Functional role of Runx3 in the regulation of aggrecan expression during cartilage development","volume":"228","author":"Wigner","year":"2013","journal-title":"J. Cell Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1126\/science.1215157","article-title":"A stem cell-based approach to cartilage repair","volume":"336","author":"Johnson","year":"2012","journal-title":"Science"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Che, X., Jin, X., Park, N.R., Kim, H.J., Kyung, H.S., Kim, H.J., Lian, J.B., Stein, J.L., Stein, G.S., and Choi, J.Y. (2023). Cbf\u03b2 Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-\u03b2 Signaling. Cells, 12.","DOI":"10.20944\/preprints202302.0284.v1"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e95640","DOI":"10.7554\/eLife.95640","article-title":"Cbfbeta regulates Wnt\/beta-catenin, Hippo\/Yap, and Tgfbeta signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis","volume":"13","author":"Chen","year":"2024","journal-title":"Elife"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Li, G., Zhang, M., Huang, Y., Yang, J., Dong, L., Shi, H., Li, L., Liu, R., and Li, J. (2021). The relationship between abnormal Core binding factor-\u03b2 expression in human cartilage and osteoarthritis. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04043-9"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:00:22Z","timestamp":1760112022000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,20]]},"references-count":147,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms251810102"],"URL":"https:\/\/doi.org\/10.3390\/ijms251810102","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,20]]}}}