Komori T (2010) Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res 339:189–195

CAS  PubMed  Google Scholar 

Ohba S (2020) Hedgehog signaling in skeletal development: roles of indian hedgehog and the mode of its action. Int J Mol Sci 21:6665

CAS  PubMed  PubMed Central  Google Scholar 

Kobayashi Y, Uehara S, Udagawa N, Takahashi N (2016) Regulation of bone metabolism by Wnt signals. J Biochem 159:387–392

CAS  PubMed  Google Scholar 

Komori T (2022) Whole aspect of Runx2 functions in skeletal development. Int J Mol Sci 23:5776

CAS  PubMed  PubMed Central  Google Scholar 

Hojo H, Ohba S, He X, Lai LP, McMahon AP (2016) Sp7/Osterix is restricted to bone-forming vertebrates where it acts as a Dlx Co-factor in osteoblast specification. Dev Cell 37:238–253

CAS  PubMed  PubMed Central  Google Scholar 

Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771

CAS  PubMed  Google Scholar 

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764

CAS  PubMed  Google Scholar 

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29

CAS  PubMed  Google Scholar 

St-Jacques B, Hammerschmidt M, McMahon AP (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 13:2072–2086

CAS  PubMed  PubMed Central  Google Scholar 

Chung UI, Schipani E, McMahon AP, Kronenberg HM (2001) Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. J Clin Investig 107:295–304

CAS  PubMed  PubMed Central  Google Scholar 

Long F, Chung UI, Ohba S, McMahon J, Kronenberg HM, McMahon AP (2004) Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development 131:1309–1318

CAS  PubMed  Google Scholar 

Rodda SJ, McMahon AP (2006) Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133:3231–3244

CAS  PubMed  Google Scholar 

Kawane T, Komori H, Liu W, Moriishi T, Miyazaki T, Mori M, Matsuo Y, Takada Y, Izumi S, Jiang Q, Nishimura R, Kawai Y, Komori T (2014) Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression. J Bone Miner Res 29:1960–1969

CAS  PubMed  Google Scholar 

Qin X, Jiang Q, Miyazaki T, Komori T (2019) Runx2 regulates cranial suture closure by inducing hedgehog, Fgf, Wnt and Pthlh signaling pathway gene expressions in suture mesenchymal cells. Hum Mol Genet 28:896–911

CAS  PubMed  Google Scholar 

Kawane T, Qin X, Jiang Q, Miyazaki T, Komori H, Yoshida CA, Matsuura-Kawata V, Sakane C, Matsuo Y, Nagai K, Maeno T, Date Y, Nishimura R, Komori T (2018) Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation by regulating Fgfr2 and Fgfr3. Sci Rep 8:13551

PubMed  PubMed Central  Google Scholar 

Nishio Y, Dong Y, Paris M, O’Keefe RJ, Schwarz EM, Drissi H (2006) Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene 372:62–70

CAS  PubMed  Google Scholar 

Yoshida CA, Komori H, Maruyama Z, Miyazaki T, Kawasaki K, Furuichi T, Fukuyama R, Mori M, Yamana K, Nakamura K, Liu W, Toyosawa S, Moriishi T, Kawaguchi H, Takada K, Komori T (2012) SP7 inhibits osteoblast differentiation at a late stage in mice. PLoS One 7:e32364

CAS  PubMed  PubMed Central  Google Scholar 

Nishimura R, Wakabayashi M, Hata K, Matsubara T, Honma S, Wakisaka S, Kiyonari H, Shioi G, Yamaguchi A, Tsumaki N, Akiyama H, Yoneda T (2012) Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase 13 (MMP13) expression in association with transcription factor Runx2 during endochondral ossification. J Biol Chem 287:33179–33190

CAS  PubMed  PubMed Central  Google Scholar 

Hojo H, Saito T, He X, Guo Q, Onodera S, Azuma T, Koebis M, Nakao K, Aiba A, Seki M, Suzuki Y, Okada H, Tanaka S, Chung UI, McMahon AP, Ohba S (2022) Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages. Cell Rep 40:111315

CAS  PubMed  PubMed Central  Google Scholar 

Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739–750

CAS  PubMed  Google Scholar 

Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727–738

CAS  PubMed  Google Scholar 

Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60

CAS  PubMed  Google Scholar 

Maeno T, Moriishi T, Yoshida CA, Komori H, Kanatani N, Izumi S, Takaoka K, Komori T (2011) Early onset of Runx2 expression caused craniosynostosis, ectopic bone formation, and limb defects. Bone 49:673–682

CAS  PubMed  Google Scholar 

Robledo RF, Rajan L, Li X, Lufkin T (2002) The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev 16:1089–1101

CAS  PubMed  PubMed Central  Google Scholar 

Pratap J, Galindo M, Zaidi SK, Vradii D, Bhat BM, Robinson JA, Choi J-Y, Komori T, Stein JL, Lian JB (2003) Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts. Can Res 63:5357–5362

CAS  Google Scholar 

Qin X, Jiang Q, Komori H, Sakane C, Fukuyama R, Matsuo Y, Ito K, Miyazaki T, Komori T (2021) Runt-related transcription factor-2 (Runx2) is required for bone matrix protein gene expression in committed osteoblasts in mice. J Bone Miner Res 36:2081–2095

CAS  PubMed  Google Scholar 

Jiang Q, Moriishi T, Komori H, Sakane C, Matsuo Y, Zhang Z, Nishimura R, Ito K, Qin X, Komori T (2024) Roles of Sp7 in osteoblasts for the proliferation, differentiation, and osteocyte process formation. J Orthop Transl 47:161–175

Google Scholar 

Nusse R, Clevers H (2017) Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169:985–999

CAS  PubMed  Google Scholar 

Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA 2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303–314

CAS  PubMed  PubMed Central  Google Scholar 

Komori T (2020) Functions of osteocalcin in bone, pancreas, testis, and muscle. Int J Mol Sci 21:7513

CAS  PubMed  PubMed Central  Google Scholar 

Diegel CR, Hann S, Ayturk UM, Hu JCW, Lim KE, Droscha CJ, Madaj ZB, Foxa GE, Izaguirre I, Transgenics Core VVA, Paracha N, Pidhaynyy B, Dowd TL, Robling AG, Warman ML, Williams BO (2020) An osteocalcin-deficient mouse strain without endocrine abnormalities. PLoS Genet 16:e1008361

CAS  PubMed  PubMed Central  Google Scholar 

Moriishi T, Ozasa R, Ishimoto T, Nakano T, Hasegawa T, Miyazaki T, Liu W, Fukuyama R, Wang Y, Komori H, Qin X, Amizuka N, Komori T (2020) Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. PLoS Genet 16:e1008586

CAS  PubMed  PubMed Central  Google Scholar 

Sun J, Hu L, Bok S, Yallowitz AR, Cung M et al (2023) A vertebral skeletal stem cell lineage driving metastasis. Nature 621:602–609

CAS  PubMed  PubMed Central  Google Scholar 

Baek WY, de Crombrugghe B, Kim JE (2010) Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance. Bone 46:920–928

CAS