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Gene Review

Runx2  -  runt-related transcription factor 2

Rattus norvegicus

Synonyms: CBF-alpha-1, Cbfa1, Core-binding factor subunit alpha-1, OSF-2, Osf2, ...
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Disease relevance of Runx2


High impact information on Runx2

  • Here, we have combined transient-overexpression, coimmunoprecipitation, in situ colocalization, chromatin immunoprecipitation, and glutathione S-transferase pull-down analyses to demonstrate that in osteoblastic cells expressing OC, VDR interacts directly with Runx2 bound to site B, which is located immediately adjacent to the VDRE [3].
  • This mechanism involves the intersection of two major pathways: Runx2, a "master" transcriptional regulator of osteoblast differentiation, and 1alpha,25-dihydroxyvitamin D3, a hormone that promotes expression of genes associated with these terminally differentiated bone cells [3].
  • Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells [3].
  • Together, our results indicate that Runx2 plays a key role in the 1alpha,25-dihydroxyvitamin D3-dependent stimulation of the OC promoter in osteoblastic cells by further stabilizing the interaction of the VDR with the VDRE [3].
  • This stimulatory effect requires intact Runx2/Cbfa1 binding sites and the vitamin D-responsive element [4].

Biological context of Runx2


Anatomical context of Runx2

  • TNAP-positive cells in the dental follicle localized nearer to alveolar bone than Runx2-positive cells [7].
  • We tested the hypothesis that Runx2 is responsible for signaling chondrocyte maturation and endochondral ossification in the condyle during mandibular advancement [5].
  • Thus, Runx2 mediates chondrocyte terminal maturation and endochondral ossification in the mandibular condyle in response to mandibular advancement [5].
  • To address these limitations, retroviral gene delivery was used to examine the effects of sustained and elevated expression of the Runx2 osteoblastic transcription factor on osteoblastic gene and protein expression and mineralization in primary rat bone marrow stromal cells [8].
  • Here we investigated whether and to what extent the MAPK (JNK/ERK)-AP-1/Runx2 signaling pathways are engaged in this phenomenon, and assessed their involvement in the functional biology of articular cartilage [9].

Associations of Runx2 with chemical compounds

  • Runx2 integrates estrogen activity in osteoblasts [10].
  • Unlike the stimulatory effect of estrogen and the inhibitory effect of glucocorticoid, androgen fails to increase Runx2 activity, whereas Runx2 potently suppresses gene expression induced by all three steroids [10].
  • Osteoblast differentiation markers (Runx2, collagen alpha1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR [11].
  • Additionally, the transcriptional co-activator p300 is recruited to the OC promoter by Runx2 where it up-regulates both basal and 1alpha,25-dihydroxy Vitamin D3-enhanced OC expression [12].
  • These additive effects suggest complementary interactions between Runx2 and dexamethasone-responsive regulatory factors [8].

Physical interactions of Runx2

  • Consistent with this interaction, the stimulatory effect of estrogen on Runx2 activity is lost when the DNA binding domain of the estrogen receptor is eliminated [10].
  • C/EBPdelta gene promoter activity was reduced by mutating the Runx binding sequence or by co-transfecting with Runx2 antisense expression plasmid, and was enhanced by overexpression of Runx-2 [1].

Regulatory relationships of Runx2

  • The isoform Runx2 (previously termed CBFa1) is highly expressed by osteoblasts and regulates expression of the TGF-beta receptor I in these cells [13].
  • In conclusion, this study demonstrates that BMP-2 and TGFbeta1 suppress collagenase-3 promoter activity in osteoblasts and establishes a link between BMP-2 action and collagenase-3 expression via Runx2, a major regulator of osteoblast formation and function [14].

Other interactions of Runx2

  • We further identified ligand-independent physical interaction between Smad2 and Runx2 [15].
  • Cotransfection of Smad2 and Runx2 constructs had a cooperative effect on TGF-beta 1-stimulated collagenase-3 promoter activity in these cells [15].
  • We have shown for the first time that Runx2 (a bone transcription factor and a potential substrate for the MAPK pathway) is phosphorylated in response to TGF-beta 1 treatment in osteoblastic cells [15].
  • This interaction contributes significantly to 1alpha,25-dihydroxyvitamin D3-dependent enhancement of the OC promoter and requires a region located C terminal to the runt homology DNA binding domain of Runx2 and the N-terminal region of VDR [3].
  • Estrogen receptor and Runx2 can be collected by co-immunoprecipitation [10].

Analytical, diagnostic and therapeutic context of Runx2


  1. Runt domain factor (Runx)-dependent effects on CCAAT/ enhancer-binding protein delta expression and activity in osteoblasts. McCarthy, T.L., Ji, C., Chen, Y., Kim, K.K., Imagawa, M., Ito, Y., Centrella, M. J. Biol. Chem. (2000) [Pubmed]
  2. Altered Cbfa1 expression and biomineralization in an osteosarcoma cell line. Perinpanayagam, H., Schneider, G., Holtman, K., Zaharias, R., Stanford, C. J. Orthop. Res. (2004) [Pubmed]
  3. Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells. Paredes, R., Arriagada, G., Cruzat, F., Villagra, A., Olate, J., Zaidi, K., van Wijnen, A., Lian, J.B., Stein, G.S., Stein, J.L., Montecino, M. Mol. Cell. Biol. (2004) [Pubmed]
  4. Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Sierra, J., Villagra, A., Paredes, R., Cruzat, F., Gutierrez, S., Javed, A., Arriagada, G., Olate, J., Imschenetzky, M., Van Wijnen, A.J., Lian, J.B., Stein, G.S., Stein, J.L., Montecino, M. Mol. Cell. Biol. (2003) [Pubmed]
  5. Runx2 regulates endochondral ossification in condyle during mandibular advancement. Tang, G.H., Rabie, A.B. J. Dent. Res. (2005) [Pubmed]
  6. Characterization of a novel KRAB/C2H2 zinc finger transcription factor involved in bone development. Jheon, A.H., Ganss, B., Cheifetz, S., Sodek, J. J. Biol. Chem. (2001) [Pubmed]
  7. Immunohistochemical Localization of {alpha}-Smooth Muscle Actin During Rat Molar Tooth Development. Hosoya, A., Nakamura, H., Ninomiya, T., Yoshiba, K., Yoshiba, N., Nakaya, H., Wakitani, S., Yamada, H., Kasahara, E., Ozawa, H. J. Histochem. Cytochem. (2006) [Pubmed]
  8. Exogenous Runx2 expression enhances in vitro osteoblastic differentiation and mineralization in primary bone marrow stromal cells. Byers, B.A., García, A.J. Tissue engineering. (2004) [Pubmed]
  9. JNK/ERK-AP-1/Runx2 induction "paves the way" to cartilage load-ignited chondroblastic differentiation. Papachristou, D.J., Pirttiniemi, P., Kantomaa, T., Papavassiliou, A.G., Basdra, E.K. Histochem. Cell Biol. (2005) [Pubmed]
  10. Runx2 integrates estrogen activity in osteoblasts. McCarthy, T.L., Chang, W.Z., Liu, Y., Centrella, M. J. Biol. Chem. (2003) [Pubmed]
  11. Ghrelin directly regulates bone formation. Fukushima, N., Hanada, R., Teranishi, H., Fukue, Y., Tachibana, T., Ishikawa, H., Takeda, S., Takeuchi, Y., Fukumoto, S., Kangawa, K., Nagata, K., Kojima, M. J. Bone Miner. Res. (2005) [Pubmed]
  12. The Runx2 transcription factor plays a key role in the 1alpha,25-dihydroxy Vitamin D3-dependent upregulation of the rat osteocalcin (OC) gene expression in osteoblastic cells. Paredes, R., Arriagada, G., Cruzat, F., Olate, J., Van Wijnen, A., Lian, J., Stein, G., Stein, J., Montecino, M. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  13. Control and counter-control of TGF-beta activity through FAST and Runx (CBFa) transcriptional elements in osteoblasts. Ji, C., Eickelberg, O., McCarthy, T.L., Centrella, M. Endocrinology (2001) [Pubmed]
  14. Bone morphogenetic protein-2 suppresses collagenase-3 promoter activity in osteoblasts through a runt domain factor 2 binding site. Varghese, S., Rydziel, S., Canalis, E. J. Cell. Physiol. (2005) [Pubmed]
  15. Transforming growth factor-beta 1 regulation of collagenase-3 expression in osteoblastic cells by cross-talk between the Smad and MAPK signaling pathways and their components, Smad2 and Runx2. Selvamurugan, N., Kwok, S., Alliston, T., Reiss, M., Partridge, N.C. J. Biol. Chem. (2004) [Pubmed]
  16. Transforming growth factor beta2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma. Ahdjoudj, S., Lasmoles, F., Holy, X., Zerath, E., Marie, P.J. J. Bone Miner. Res. (2002) [Pubmed]
  17. Synergy between genetic and tissue engineering: Runx2 overexpression and in vitro construct development enhance in vivo mineralization. Byers, B.A., Guldberg, R.E., García, A.J. Tissue engineering. (2004) [Pubmed]
  18. Strong and rapid induction of osteoblast differentiation by Cbfa1/Til-1 overexpression for bone regeneration. Kojima, H., Uemura, T. J. Biol. Chem. (2005) [Pubmed]
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