This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamaguchi, A. Articles by Suda, T. Search for Related Content PubMed PubMed Citation Articles by Yamaguchi, A. Articles by Suda, T.

Regulation of Osteoblast Differentiation Mediated by Bone Morphogenetic Proteins, Hedgehogs, and Cbfa1

Department of Oral Pathology (A.Y.), Nagasaki University School of Dentistry, 1–7-1 Sakamoto, Nagasaki 852, Department of Molecular Medicine (T.K.), School of Medicine, Osaka University, 2–2 Yamada-oka, Suita, Osaka 565 and "Form and Function", PRESTO, Japan Science and Technology Corporation, and Department of Biochemistry (T.S.), School of Dentistry, Showa University, 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan

Osteoblasts arise from common progenitors with chondrocytes, muscle and adipocytes, and various hormones and local factors regulate their differentiation. We review here regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor -1 (Cbfa1). BMPs are the most potent regulators of osteoblast differentiation among the local factors. Sonic and Indian hedgehogs are involved in osteoblast differentiation by interacting with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in the processes of a determination of osteoblast cell lineage and maturation of osteoblasts. Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation, because Cbfa1-deficient mice completely lacked bone formation due to maturation arrest of osteoblasts. Although the regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are an important local factor that up-regulates Cbfa1 expression. Thus, the intimate interaction between local factors such as BMPs and hedgehogs and the transcription factor, Cbfa1, is important to osteoblast differentiation and bone formation.

This article has been cited by other articles:

				T. Endo, K. Ohta, and T. Kobayashi Expression and Function of Cbfa-1/Runx2 in Thyroid Papillary Carcinoma Cells J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2409 - 2412. [Abstract] [Full Text] [PDF]

				A. Abzhanov, S. J. Rodda, A. P. McMahon, and C. J. Tabin Regulation of skeletogenic differentiation in cranial dermal bone Development, September 1, 2007; 134(17): 3133 - 3144. [Abstract] [Full Text] [PDF]

				K. Watanabe, H. Tsuchiya, K. Sakurakichi, and K. Tomita Bone transport using hydroxyapatite loaded with bone morphogenetic protein in rabbits J Bone Joint Surg Br, August 1, 2007; 89-B(8): 1122 - 1129. [Abstract] [Full Text] [PDF]

				A. Shimoyama, M. Wada, F. Ikeda, K. Hata, T. Matsubara, A. Nifuji, M. Noda, K. Amano, A. Yamaguchi, R. Nishimura, et al. Ihh/Gli2 Signaling Promotes Osteoblast Differentiation by Regulating Runx2 Expression and Function Mol. Biol. Cell, July 1, 2007; 18(7): 2411 - 2418. [Abstract] [Full Text] [PDF]

				Y. Luan, X.-P. Yu, K. Xu, B. Ding, J. Yu, Y. Huang, N. Yang, P. Lengyel, P. E. Di Cesare, and C.-j. Liu The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity J. Biol. Chem., June 8, 2007; 282(23): 16860 - 16870. [Abstract] [Full Text] [PDF]

				Y. Yamamoto, N. Udagawa, S. Matsuura, Y. Nakamichi, H. Horiuchi, A. Hosoya, M. Nakamura, H. Ozawa, K. Takaoka, J. M. Penninger, et al. Osteoblasts Provide a Suitable Microenvironment for the Action of Receptor Activator of Nuclear Factor-{kappa}B Ligand Endocrinology, July 1, 2006; 147(7): 3366 - 3374. [Abstract] [Full Text] [PDF]

				D. Vernet, G. Nolazco, L. Cantini, T. R. Magee, A. Qian, J. Rajfer, and N. F. Gonzalez-Cadavid Evidence That Osteogenic Progenitor Cells in the Human Tunica Albuginea May Originate from Stem Cells: Implications for Peyronie Disease Biol Reprod, December 1, 2005; 73(6): 1199 - 1210. [Abstract] [Full Text] [PDF]

				A. Nakashima, T. Katagiri, and M. Tamura Cross-talk between Wnt and Bone Morphogenetic Protein 2 (BMP-2) Signaling in Differentiation Pathway of C2C12 Myoblasts J. Biol. Chem., November 11, 2005; 280(45): 37660 - 37668. [Abstract] [Full Text] [PDF]

				T. Oshima, M. Abe, J. Asano, T. Hara, K. Kitazoe, E. Sekimoto, Y. Tanaka, H. Shibata, T. Hashimoto, S. Ozaki, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 Blood, November 1, 2005; 106(9): 3160 - 3165. [Abstract] [Full Text] [PDF]

				T. Morgan, G. J. Atkins, M. K. Trivett, S. A. Johnson, M. Kansara, S. L. Schlicht, J. L. Slavin, P. Simmons, I. Dickinson, G. Powell, et al. Molecular Profiling of Giant Cell Tumor of Bone and the Osteoclastic Localization of Ligand for Receptor Activator of Nuclear Factor {kappa}B Am. J. Pathol., July 1, 2005; 167(1): 117 - 128. [Abstract] [Full Text] [PDF]

				S Toyran, A Y Lin, and D P Edward Expression of growth differentiation factor-5 and bone morphogenic protein-7 in intraocular osseous metaplasia Br. J. Ophthalmol., July 1, 2005; 89(7): 885 - 890. [Abstract] [Full Text] [PDF]

				D.D. Bosshardt Are Cementoblasts a Subpopulation of Osteoblasts or a Unique Phenotype? J. Dent. Res., May 1, 2005; 84(5): 390 - 406. [Abstract] [Full Text] [PDF]

				K. Hata, R. Nishimura, M. Ueda, F. Ikeda, T. Matsubara, F. Ichida, K. Hisada, T. Nokubi, A. Yamaguchi, and T. Yoneda A CCAAT/Enhancer Binding Protein {beta} Isoform, Liver-Enriched Inhibitory Protein, Regulates Commitment of Osteoblasts and Adipocytes Mol. Cell. Biol., March 1, 2005; 25(5): 1971 - 1979. [Abstract] [Full Text] [PDF]

				C.-j. Liu, E. Chang, J. Yu, C. S. Carlson, L. Prazak, X.-P. Yu, B. Ding, P. Lengyel, and P. E. D. Cesare The Interferon-inducible p204 Protein Acts as a Transcriptional Coactivator of Cbfa1 and Enhances Osteoblast Differentiation J. Biol. Chem., January 28, 2005; 280(4): 2788 - 2796. [Abstract] [Full Text] [PDF]

				M. I. Reinhold, M. Abe, R. M. Kapadia, Z. Liao, and M. C. Naski FGF18 Represses Noggin Expression and Is Induced by Calcineurin J. Biol. Chem., September 10, 2004; 279(37): 38209 - 38219. [Abstract] [Full Text] [PDF]

				L. Mejia-Luna and G. Avila Ca2+ channel regulation by transforming growth factor-{beta}1 and bone morphogenetic protein-2 in developing mice myotubes J. Physiol., August 15, 2004; 559(1): 41 - 54. [Abstract] [Full Text] [PDF]

				F. Ichida, R. Nishimura, K. Hata, T. Matsubara, F. Ikeda, K. Hisada, H. Yatani, X. Cao, T. Komori, A. Yamaguchi, et al. Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation J. Biol. Chem., August 6, 2004; 279(32): 34015 - 34022. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				O. L. Sierra, S.-L. Cheng, A. P. Loewy, N. Charlton-Kachigian, and D. A. Towler MINT, the Msx2 Interacting Nuclear Matrix Target, Enhances Runx2-dependent Activation of the Osteocalcin Fibroblast Growth Factor Response Element J. Biol. Chem., July 30, 2004; 279(31): 32913 - 32923. [Abstract] [Full Text] [PDF]

				X.-D. CHEN, L. W. FISHER, P. G. ROBEY, and M. F. YOUNG The small leucine-rich proteoglycan biglycan modulates BMP-4-induced osteoblast differentiation FASEB J, June 1, 2004; 18(9): 948 - 958. [Abstract] [Full Text] [PDF]

				M. Komaki, A. Asakura, M. A. Rudnicki, J. Sodek, and S. Cheifetz MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures J. Cell Sci., March 15, 2004; 117(8): 1457 - 1468. [Abstract] [Full Text] [PDF]

				E. Hay, J. Lemonnier, O. Fromigue, H. Guenou, and P. J. Marie Bone Morphogenetic Protein Receptor IB Signaling Mediates Apoptosis Independently of Differentiation in Osteoblastic Cells J. Biol. Chem., January 16, 2004; 279(3): 1650 - 1658. [Abstract] [Full Text] [PDF]

				T. Aberg, A. Cavender, J. S. Gaikwad, A. L.J.J. Bronckers, X. Wang, J. Waltimo-Siren, I. Thesleff, and R. N. D'Souza Phenotypic Changes in Dentition of Runx2 Homozygote-null Mutant Mice J. Histochem. Cytochem., January 1, 2004; 52(1): 131 - 140. [Abstract] [Full Text] [PDF]

				J. Melrose, S. Smith, P. Ghosh, and J. Whitelock Perlecan, the Multidomain Heparan Sulfate Proteoglycan of Basement Membranes, Is also a Prominent Component of the Cartilaginous Primordia in the Developing Human Fetal Spine J. Histochem. Cytochem., October 1, 2003; 51(10): 1331 - 1341. [Abstract] [Full Text] [PDF]

				H. Cheng, W. Jiang, F. M. Phillips, R. C. Haydon, Y. Peng, L. Zhou, H. H. Luu, N. An, B. Breyer, P. Vanichakarn, et al. Osteogenic Activity of the Fourteen Types of Human Bone Morphogenetic Proteins (BMPs) J. Bone Joint Surg. Am., August 1, 2003; 85(8): 1544 - 1552. [Abstract] [Full Text] [PDF]

				K.-i. Hirose, H. Tomiyama, R. Okazaki, T. Arai, Y. Koji, G. Zaydun, S. Hori, and A. Yamashina Increased Pulse Wave Velocity Associated with Reduced Calcaneal Quantitative Osteo-sono Index: Possible Relationship Between Atherosclerosis and Osteopenia J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2573 - 2578. [Abstract] [Full Text] [PDF]

				H. Sowa, H. Kaji, L. Canaff, G. N. Hendy, T. Tsukamoto, T. Yamaguchi, K. Miyazono, T. Sugimoto, and K. Chihara Inactivation of Menin, the Product of the Multiple Endocrine Neoplasia Type 1 Gene, Inhibits the Commitment of Multipotential Mesenchymal Stem Cells into the Osteoblast Lineage J. Biol. Chem., May 30, 2003; 278(23): 21058 - 21069. [Abstract] [Full Text] [PDF]

				H. Qi, D. J. Aguiar, S. M. Williams, A. La Pean, W. Pan, and C. M. Verfaillie Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells PNAS, March 18, 2003; 100(6): 3305 - 3310. [Abstract] [Full Text] [PDF]

				Y. Takeuchi, S. Watanabe, G. Ishii, S. Takeda, K. Nakayama, S. Fukumoto, Y. Kaneta, D. Inoue, T. Matsumoto, K. Harigaya, et al. Interleukin-11 as a Stimulatory Factor for Bone Formation Prevents Bone Loss with Advancing Age in Mice J. Biol. Chem., December 6, 2002; 277(50): 49011 - 49018. [Abstract] [Full Text] [PDF]

				A. L. Hager-Theodorides, S. V. Outram, D. K. Shah, R. Sacedon, R. E. Shrimpton, A. Vicente, A. Varas, and T. Crompton Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation J. Immunol., November 15, 2002; 169(10): 5496 - 5504. [Abstract] [Full Text] [PDF]

				D. M. Willis, A. P. Loewy, N. Charlton-Kachigian, J.-S. Shao, D. M. Ornitz, and D. A. Towler Regulation of Osteocalcin Gene Expression by a Novel Ku Antigen Transcription Factor Complex J. Biol. Chem., September 27, 2002; 277(40): 37280 - 37291. [Abstract] [Full Text] [PDF]

				M. Hadjiargyrou, F. Lombardo, S. Zhao, W. Ahrens, J. Joo, H. Ahn, M. Jurman, D. W. White, and C. T. Rubin Transcriptional Profiling of Bone Regeneration. INSIGHT INTO THE MOLECULAR COMPLEXITY OF WOUND REPAIR J. Biol. Chem., August 9, 2002; 277(33): 30177 - 30182. [Abstract] [Full Text] [PDF]

				D. M. Ornitz and P. J. Marie FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease Genes & Dev., June 15, 2002; 16(12): 1446 - 1465. [Full Text] [PDF]

				R. Okazaki, D. Inoue, M. Shibata, M. Saika, S. Kido, H. Ooka, H. Tomiyama, Y. Sakamoto, and T. Matsumoto Estrogen Promotes Early Osteoblast Differentiation and Inhibits Adipocyte Differentiation in Mouse Bone Marrow Stromal Cell Lines that Express Estrogen Receptor (ER) {alpha} or {beta} Endocrinology, June 1, 2002; 143(6): 2349 - 2356. [Abstract] [Full Text] [PDF]

				W. Liu, S. Toyosawa, T. Furuichi, N. Kanatani, C. Yoshida, Y. Liu, M. Himeno, S. Narai, A. Yamaguchi, and T. Komori Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures J. Cell Biol., October 1, 2001; 155(1): 157 - 166. [Abstract] [Full Text] [PDF]

				J. Yang, K. Fizazi, S. Peleg, C. R. Sikes, A. K. Raymond, N. Jamal, M. Hu, M. Olive, L. A. Martinez, C. G. Wood, et al. Prostate Cancer Cells Induce Osteoblast Differentiation through a Cbfa1-dependent Pathway Cancer Res., July 1, 2001; 61(14): 5652 - 5659. [Abstract] [Full Text] [PDF]

				R. Gruber, C. Mayer, K. Bobacz, M.-T. Krauth, W. Graninger, F. P. Luyten, and L. Erlacher Effects of Cartilage-Derived Morphogenetic Proteins and Osteogenic Protein-1 on Osteochondrogenic Differentiation of Periosteum-Derived Cells Endocrinology, May 1, 2001; 142(5): 2087 - 2094. [Abstract] [Full Text]