Transcription factors controlling osteoblastogenesis.

The recent development of molecular biology and mouse genetics and the analysis of the skeletal phenotype induced by genetic mutations in humans led to a better understanding of the role of transcription factors that govern bone formation. This review summarizes the role of transcription factors in osteoblastogenesis and provides an integrated perspective on how the activities of multiple classes of factors are coordinated for the complex process of developing the osteoblast phenotype. The roles of Runx2, the principal transcriptional regulator of osteoblast differentiation, Osterix, beta-Catenin and ATF which act downstream of Runx2, and other transcription factors that contribute to the control of osteoblastogenesis including the AP1, C/EBPs, PPARgamma and homeodomain, helix-loop-helix proteins are discussed. This review also updates the regulation of transcription factor expression by signaling factors and hormones that control osteoblastogenesis.

[1]  I. Gérin,et al.  Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ* , 2007, Journal of Biological Chemistry.

[2]  N. Kanatani,et al.  Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures , 2001, The Journal of cell biology.

[3]  D. Ron,et al.  ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. , 2006, Cell metabolism.

[4]  P. Lengyel,et al.  The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity* , 2007, Journal of Biological Chemistry.

[5]  B. Frenkel,et al.  Stage-specific expression of Dlx-5 during osteoblast differentiation: involvement in regulation of osteocalcin gene expression. , 1997, Molecular endocrinology.

[6]  M. Justice,et al.  A twist code determines the onset of osteoblast differentiation. , 2004, Developmental cell.

[7]  E. Wagner,et al.  The Fos‐related antigen Fra‐1 is an activator of bone matrix formation , 2004, The EMBO journal.

[8]  Remo Guidieri.  Res , 1995, RES: Anthropology and Aesthetics.

[9]  T. Taniguchi,et al.  Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. , 2003, Genes & development.

[10]  Stephen N. Jones,et al.  Osteoblast differentiation and skeletal development are regulated by Mdm2–p53 signaling , 2006, The Journal of cell biology.

[11]  P. Marie,et al.  Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome. , 2001, The Journal of clinical investigation.

[12]  J. Westendorf.  Transcriptional co‐repressors of Runx2 , 2006, Journal of cellular biochemistry.

[13]  C. Dufour,et al.  Down-regulation of ubiquitin ligase Cbl induced by twist haploinsufficiency in Saethre-Chotzen syndrome results in increased PI3K/Akt signaling and osteoblast proliferation. , 2006, The American journal of pathology.

[14]  P. Sassone-Corsi,et al.  ATF4 Is a Substrate of RSK2 and an Essential Regulator of Osteoblast Biology Implication for Coffin-Lowry Syndrome , 2004, Cell.

[15]  D. Ornitz,et al.  Sequential roles of Hedgehog and Wnt signaling in osteoblast development , 2004, Development.

[16]  M. Centrella,et al.  Links among growth factors, hormones, and nuclear factors with essential roles in bone formation. , 2000, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[17]  K. Miyazono,et al.  Lack of Schnurri-2 Expression Associates with Reduced Bone Remodeling and Osteopenia* , 2007, Journal of Biological Chemistry.

[18]  J. Westendorf,et al.  Histone Deacetylase 3 Interacts with Runx2 to Repress the Osteocalcin Promoter and Regulate Osteoblast Differentiation* , 2004, Journal of Biological Chemistry.

[19]  A. Geiser,et al.  Parathyroid hormone bone anabolic action requires Cbfa1/Runx2-dependent signaling. , 2003, Molecular endocrinology.

[20]  P. Marie,et al.  c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-beta in osteoblastic cells. , 1995, Molecular endocrinology.

[21]  T. Fujita,et al.  Core-binding factor β interacts with Runx2 and is required for skeletal development , 2002, Nature Genetics.

[22]  Xizhi Guo,et al.  Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. , 2005, Developmental cell.

[23]  Thomas Benjamin,et al.  TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation , 2005, Science.

[24]  P. Marie,et al.  A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. , 2005, Human molecular genetics.

[25]  J. Westendorf,et al.  Histone Deacetylase Inhibitors Promote Osteoblast Maturation , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[27]  M. Noda,et al.  Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo. , 2006, Endocrinology.

[28]  G. Stein,et al.  CCAAT/Enhancer-binding Proteins (C/EBP) β and δ Activate Osteocalcin Gene Transcription and Synergize with Runx2 at the C/EBP Element to Regulate Bone-specific Expression* , 2002, The Journal of Biological Chemistry.

[29]  R. Derynck,et al.  Repression of Runx2 function by TGF‐β through recruitment of class II histone deacetylases by Smad3 , 2005, The EMBO journal.

[30]  E. Wagner,et al.  Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1 , 2000, Nature Medicine.

[31]  Su‐Li Cheng,et al.  Msx2 Promotes Osteogenesis and Suppresses Adipogenic Differentiation of Multipotent Mesenchymal Progenitors* , 2003, Journal of Biological Chemistry.

[32]  G. Stein,et al.  The Runx2 transcription factor plays a key role in the 1α,25-dihydroxy Vitamin D3-dependent upregulation of the rat osteocalcin (OC) gene expression in osteoblastic cells , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[33]  H. Ryoo,et al.  The suppressive effect of myeloid elf‐1‐like factor (MEF) in osteogenic differentiation , 2007, Journal of cellular physiology.

[34]  H. Yatani,et al.  Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation* , 2004, Journal of Biological Chemistry.

[35]  S. Mundlos,et al.  Cbfa1, a Candidate Gene for Cleidocranial Dysplasia Syndrome, Is Essential for Osteoblast Differentiation and Bone Development , 1997, Cell.

[36]  Hyo-Sang Park,et al.  BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. , 2003, Biochemical and biophysical research communications.

[37]  H. Shibuya,et al.  Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5 , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[38]  J. Wozney,et al.  Dlx5 Specifically Regulates Runx2 Type II Expression by Binding to Homeodomain-response Elements in the Runx2 Distal Promoter* , 2005, Journal of Biological Chemistry.

[39]  S. K. Zaidi,et al.  Tyrosine phosphorylation controls Runx2‐mediated subnuclear targeting of YAP to repress transcription , 2004, The EMBO journal.

[40]  Masaki Noda,et al.  Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function. , 2007, Molecular biology of the cell.

[41]  B. Frenkel,et al.  Glucocorticoids Inhibit the Transcriptional Activity of LEF/TCF in Differentiating Osteoblasts in a Glycogen Synthase Kinase-3β-dependent and -independent Manner* , 2005, Journal of Biological Chemistry.

[42]  Wei-zhong Chang,et al.  Runx2 Integrates Estrogen Activity in Osteoblasts* , 2003, Journal of Biological Chemistry.

[43]  V. Lefebvre,et al.  Regulatory mechanisms in the pathways of cartilage and bone formation. , 2001, Current opinion in cell biology.

[44]  Makoto Sato,et al.  Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts , 1997, Cell.

[45]  I. Fariñas,et al.  SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation , 2006, Cell.

[46]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[47]  P. Marie,et al.  Temporal variation of c‐fos proto‐oncogene expression during osteoblast differentiation and osteogenesis in developing rat bone , 1995, Journal of cellular biochemistry.

[48]  L. Lanyon,et al.  Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α* , 2007, Journal of Biological Chemistry.

[49]  E. Wagner,et al.  Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects , 2004, The Journal of cell biology.

[50]  Miss A.O. Penney.  (b) , 1974, The New Yale Book of Quotations.

[51]  R. Maxson,et al.  The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. , 1996, Human molecular genetics.

[52]  R. Maxson,et al.  Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans. , 1999, Developmental biology.

[53]  G. Stein,et al.  Apoptosis during bone‐like tissue development in vitro , 1998, Journal of cellular biochemistry.

[54]  T. Kerppola,et al.  Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity , 2001, Oncogene.

[55]  P. Marie.  The Molecular Genetics of Bone Formation , 2001, American journal of pharmacogenomics : genomics-related research in drug development and clinical practice.

[56]  John A. Robinson,et al.  Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts. , 2003, Cancer research.

[57]  G. Karsenty,et al.  MAPK Pathways Activate and Phosphorylate the Osteoblast-specific Transcription Factor, Cbfa1* , 2000, The Journal of Biological Chemistry.

[58]  S. K. Zaidi,et al.  Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. , 2004, Critical reviews in eukaryotic gene expression.

[59]  D. Rice,et al.  Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault , 2003, Development.

[60]  G. Karsenty,et al.  Cooperative Interactions between Activating Transcription Factor 4 and Runx2/Cbfa1 Stimulate Osteoblast-specific Osteocalcin Gene Expression* , 2005, Journal of Biological Chemistry.

[61]  G. Stein,et al.  Dlx3 Transcriptional Regulation of Osteoblast Differentiation: Temporal Recruitment of Msx2, Dlx3, and Dlx5 Homeodomain Proteins to Chromatin of the Osteocalcin Gene , 2004, Molecular and Cellular Biology.

[62]  Qiang Wu,et al.  p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling , 2006, The Journal of cell biology.

[63]  Toshihisa Komori,et al.  Regulation of osteoblast differentiation by transcription factors , 2006, Journal of cellular biochemistry.

[64]  Ayse B. Celil,et al.  BMP-2 and Insulin-like Growth Factor-I Mediate Osterix (Osx) Expression in Human Mesenchymal Stem Cells via the MAPK and Protein Kinase D Signaling Pathways* , 2005, Journal of Biological Chemistry.

[65]  A. Baldini,et al.  Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia , 1997, Nature Genetics.

[66]  K. A. Wilson,et al.  Col1a1 Promoter-targeted Expression of p20 CCAAT Enhancer-binding Protein β (C/EBPβ), a Truncated C/EBPβ Isoform, Causes Osteopenia in Transgenic Mice* , 2005, Journal of Biological Chemistry.

[67]  M. Kelz,et al.  Overexpression of ΔFosB transcription factor(s) increases bone formation and inhibits adipogenesis , 2000, Nature Medicine.

[68]  P. Roberson,et al.  Proteasomal Degradation of Runx2 Shortens Parathyroid Hormone-induced Anti-apoptotic Signaling in Osteoblasts , 2003, Journal of Biological Chemistry.

[69]  M. Glimcher,et al.  Regulation of Adult Bone Mass by the Zinc Finger Adapter Protein Schnurri-3 , 2006, Science.

[70]  S. Narumiya,et al.  Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[71]  C. Abate-Shen,et al.  Roles for Msx and Dlx homeoproteins in vertebrate development. , 2000, Gene.

[72]  Dimitris Kletsas,et al.  The Bone-specific Transcriptional Regulator Cbfa1 Is a Target of Mechanical Signals in Osteoblastic Cells* , 2002, The Journal of Biological Chemistry.

[73]  M. Wegner,et al.  The high mobility group transcription factor Sox8 is a negative regulator of osteoblast differentiation , 2005, The Journal of cell biology.

[74]  E. Wagner,et al.  Reaching a genetic and molecular understanding of skeletal development. , 2002, Developmental cell.

[75]  H. Shibuya,et al.  A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction. , 1999, Developmental biology.

[76]  M. Almeida,et al.  Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting β-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription* , 2007, Journal of Biological Chemistry.

[77]  T. Latifi,et al.  Reciprocal regulation of osteocalcin transcription by the homeodomain proteins Msx2 and Dlx5. , 1998, Biochemistry.

[78]  R. Jilka,et al.  Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARγ2 , 1999, Journal of cellular biochemistry.

[79]  E. Hinoi,et al.  Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-dependent Transcriptional Activation* , 2006, Journal of Biological Chemistry.

[80]  G. Stein,et al.  Runx2/Cbfa1: a multifunctional regulator of bone formation. , 2003, Current pharmaceutical design.

[81]  Kozo Nakamura,et al.  Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[82]  A. Jheon,et al.  Characterization of a Novel KRAB/C2H2Zinc Finger Transcription Factor Involved in Bone Development* , 2001, The Journal of Biological Chemistry.

[83]  J. Deng,et al.  The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation , 2002, Cell.

[84]  A. Monsoro-Burq,et al.  Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. , 2007, Developmental biology.

[85]  Wei Wang,et al.  Fibroblast Growth Factors Lead to Increased Msx2 Expression and Fusion in Calvarial Sutures , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[86]  Kozo Nakamura,et al.  PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. , 2004, The Journal of clinical investigation.

[87]  P. Marie,et al.  Isolation and Characterization of Human Clonogenic Osteoblast Progenitors Immunoselected from Fetal Bone Marrow Stroma Using STRO‐1 Monoclonal Antibody , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[88]  C. Glackin,et al.  TWIST, a basic helix‐loop‐helix transcription factor, can regulate the human osteogenic lineage , 1999, Journal of cellular biochemistry.

[89]  A. Papavassiliou,et al.  Growth Hormone Attenuates the Transcriptional Activity of Runx2 by Facilitating Its Physical Association With Stat3β , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[90]  Di Chen,et al.  Smurf1 Inhibits Osteoblast Differentiation and Bone Formation in Vitro and in Vivo* , 2004, Journal of Biological Chemistry.

[91]  Jae-Hyun Sung,et al.  BMP-2-induced Runx2 Expression Is Mediated by Dlx5, and TGF-β1 Opposes the BMP-2-induced Osteoblast Differentiation by Suppression of Dlx5 Expression* , 2003, Journal of Biological Chemistry.

[92]  M. Macoritto,et al.  1,25(OH)2D3 inhibits bone marrow adipogenesis in senescence accelerated mice (SAM-P/6) by decreasing the expression of peroxisome proliferator-activated receptor gamma 2 (PPARgamma2). , 2004, Experimental gerontology.

[93]  Ericka Stricklin-Parker,et al.  Ann , 2005 .

[94]  H. Ryoo,et al.  The Protein Kinase C Pathway Plays a Central Role in the Fibroblast Growth Factor-stimulated Expression and Transactivation Activity of Runx2* , 2003, The Journal of Biological Chemistry.

[95]  Monte M Winslow,et al.  Calcineurin/NFAT signaling in osteoblasts regulates bone mass. , 2006, Developmental cell.

[96]  R. Maas,et al.  Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation , 2000, Nature Genetics.

[97]  T. Lufkin,et al.  The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. , 2002, Genes & development.

[98]  Ayse B. Celil,et al.  Osx transcriptional regulation is mediated by additional pathways to BMP2/Smad signaling , 2005, Journal of cellular biochemistry.

[99]  X. Holy,et al.  Transforming Growth Factor β2 Inhibits Adipocyte Differentiation Induced by Skeletal Unloading in Rat Bone Marrow Stroma , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[100]  G. Karsenty,et al.  Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation , 1997, Cell.

[101]  G. Stein,et al.  HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genes , 2007, Molecular and Cellular Biology.

[102]  S. K. Zaidi,et al.  Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression , 2004, Oncogene.

[103]  C. Deng,et al.  A Ser250Trp substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis , 2003 .

[104]  K. Yamana,et al.  Cbfβ regulates Runx2 function isoform-dependently in postnatal bone development , 2006 .

[105]  K. Moriyama,et al.  A Soluble Form of Fibroblast Growth Factor Receptor 2 (FGFR2) with S252W Mutation Acts as an Efficient Inhibitor for the Enhanced Osteoblastic Differentiation Caused by FGFR2 Activation in Apert Syndrome* , 2004, Journal of Biological Chemistry.

[106]  G. Karsenty,et al.  ATF4, the Osteoblast Accumulation of Which Is Determined Post-translationally, Can Induce Osteoblast-specific Gene Expression in Non-osteoblastic Cells* , 2004, Journal of Biological Chemistry.

[107]  Walter Birchmeier,et al.  Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. , 2005, Developmental cell.

[108]  M. Almeida,et al.  Wnt Proteins Prevent Apoptosis of Both Uncommitted Osteoblast Progenitors and Differentiated Osteoblasts by β-Catenin-dependent and -independent Signaling Cascades Involving Src/ERK and Phosphatidylinositol 3-Kinase/AKT* , 2005, Journal of Biological Chemistry.

[109]  K. Miyazono,et al.  A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[110]  Martina I Reinhold,et al.  Direct Interactions of Runx2 and Canonical Wnt Signaling Induce FGF18* , 2006, Journal of Biological Chemistry.

[111]  V. Castronovo,et al.  Runx2- and Histone Deacetylase 3-mediated Repression Is Relieved in Differentiating Human Osteoblast Cells to Allow High Bone Sialoprotein Expression* , 2007, Journal of Biological Chemistry.

[112]  P. Bénit,et al.  Mutations of the TWIST gene in the Saethre-Chotzene syndrome , 1997, Nature Genetics.

[113]  T. Fujita,et al.  Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling , 2004, The Journal of cell biology.

[114]  B. Wang,et al.  Parathyroid hormone regulates osterix and Runx2 mRNA expression predominantly through protein kinase A signaling in osteoblast-like cells , 2006, Journal of endocrinological investigation.

[115]  C. Tribioli,et al.  The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. , 1999, Development.

[116]  G. Karsenty,et al.  Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. , 2006, Current topics in developmental biology.

[117]  H. Roca,et al.  BMP Signaling Is Required for RUNX2‐Dependent Induction of the Osteoblast Phenotype , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[118]  E. Wagner,et al.  Fos and bone cell development: lessons from a nuclear oncogene. , 1995, Trends in genetics : TIG.

[119]  T. Kodama,et al.  NFAT and Osterix cooperatively regulate bone formation , 2005, Nature Medicine.

[120]  G. Merlo,et al.  Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation , 2006, Mechanisms of Development.

[121]  K. Park,et al.  Activation of Peroxisome Proliferator-activated Receptor-γ Inhibits the Runx2-mediated Transcription of Osteocalcin in Osteoblasts* , 2003, Journal of Biological Chemistry.

[122]  M. Almeida,et al.  Induction of Osteoblast Differentiation by Selective Activation of Kinase-Mediated Actions of the Estrogen Receptor , 2006, Molecular and Cellular Biology.

[123]  J. Lemonnier,et al.  Bone Morphogenetic Protein Receptor IB Signaling Mediates Apoptosis Independently of Differentiation in Osteoblastic Cells* , 2004, Journal of Biological Chemistry.

[124]  F. Parhami,et al.  Atherogenic Diet and Minimally Oxidized Low Density Lipoprotein Inhibit Osteogenic and Promote Adipogenic Differentiation of Marrow Stromal Cells , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[125]  G. Stein,et al.  The core-binding factor β subunit is required for bone formation and hematopoietic maturation , 2002, Nature Genetics.

[126]  V. El Ghouzzi,et al.  Twist haploinsufficiency in Saethre-Chotzen syndrome induces calvarial osteoblast apoptosis due to increased TNFalpha expression and caspase-2 activation. , 2002, Human molecular genetics.

[127]  K. Chihara,et al.  Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells. , 2006, Endocrinology.

[128]  J. Wozney,et al.  Runx2 Is a Common Target of Transforming Growth Factor β1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12 , 2000, Molecular and Cellular Biology.

[129]  Brendan H. Lee,et al.  Dominance of SOX9 function over RUNX2 during skeletogenesis , 2006, Proceedings of the National Academy of Sciences.

[130]  M. Hüfner,et al.  Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin‐D3, dexamethasone, and local growth factors in primary human osteoblasts , 2002, Journal of cellular biochemistry.

[131]  M. Macoritto,et al.  1,25(OH)2D3 inhibits bone marrow adipogenesis in senescence accelerated mice (SAM-P/6) by decreasing the expression of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) , 2004, Experimental Gerontology.

[132]  Janet L Stein,et al.  Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression* , 2005, Journal of Biological Chemistry.

[133]  E. Wagner,et al.  Functions of AP1 (Fos/Jun) in bone development , 2002, Annals of the rheumatic diseases.