core binding factor alpha 1 subunit


Summary: A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION.

Top Publications

  1. Yu S, Geng Q, Sun F, Yu Y, Pan Q, Hong A. Osteogenic differentiation of C2C12 myogenic progenitor cells requires the Fos-related antigen Fra-1 - a novel target of Runx2. Biochem Biophys Res Commun. 2013;430:173-8 pubmed publisher
    ..Together, these results indicate that Fra-1 is a direct target of Runx2 during osteogenic differentiation of C2C12 myogenic progenitor cells...
  2. Niu D, Kondo T, Nakazawa T, Oishi N, Kawasaki T, Mochizuki K, et al. Transcription factor Runx2 is a regulator of epithelial-mesenchymal transition and invasion in thyroid carcinomas. Lab Invest. 2012;92:1181-90 pubmed publisher
    ..Our data suggest that enhanced Runx2 is functionally linked to tumor invasion and metastasis of thyroid carcinoma by regulating EMT-related molecules, matrix metalloproteinases and angiogenic/lymphangiogenic factors...
  3. Nishimura R, Wakabayashi M, Hata K, Matsubara T, Honma S, Wakisaka S, et al. 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. 2012;287:33179-90 pubmed
  4. Sancisi V, Borettini G, Maramotti S, Ragazzi M, Tamagnini I, Nicoli D, et al. Runx2 isoform I controls a panel of proinvasive genes driving aggressiveness of papillary thyroid carcinomas. J Clin Endocrinol Metab. 2012;97:E2006-15 pubmed publisher
    ..In a recent work, we reported that the transcriptional regulator Id1 contributes to thyroid cancer progression by powering the invasion capacity of tumor cells...
  5. Liao X, Zhang Z, Yuan K, Liu Y, Feng X, Cui R, et al. MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells. Endocrinology. 2013;154:3344-52 pubmed publisher
    ..These results demonstrate that miR-133a is a key negative regulator of the osteogenic differentiation of VSMCs. ..
  6. Wang C, Yang S, Wang Z, Tan J, Xing S, Chen D, et al. PCAF acetylates Runx2 and promotes osteoblast differentiation. J Bone Miner Metab. 2013;31:381-9 pubmed publisher
    ..ALP activity and the mineralized area were attenuated under PCAF knockdown conditions. These results indicate that PCAF is an important regulator for promoting osteoblast differentiation via acetylation modification of Runx2. ..
  7. Sinha K, Zhou X. Genetic and molecular control of osterix in skeletal formation. J Cell Biochem. 2013;114:975-84 pubmed publisher
  8. Park E, Park J, Franceschi R, Jo M. The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells. Mol Cell Endocrinol. 2012;362:165-75 pubmed publisher
    ..Together, these novel findings provide support for the role of RUNX2 in down-regulation of Runx1, Ptgs2, and Tnfaip6 during the late ovulatory period to support proper ovulation and/or luteinization...
  9. Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, et al. Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes. J Bone Miner Metab. 2013;31:53-63 pubmed publisher
    ..In conclusion, our data suggest that RA regulates commitment of MSCs into osteoblasts and adipocytes by controlling transcriptional regulators. ..

More Information


  1. Gautam J, Kushwaha P, Swarnkar G, Khedgikar V, Nagar G, Singh D, et al. EGb 761 promotes osteoblastogenesis, lowers bone marrow adipogenesis and atherosclerotic plaque formation. Phytomedicine. 2012;19:1134-42 pubmed publisher
    ..From this data, it can be implied that EGb 761 controls bone loss, adiposity and lowers atherogenic risk factor after HCD induction. ..
  2. Morrison N, Stephens A, Osato M, Polly P, Tan T, Yamashita N, et al. Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation. PLoS ONE. 2012;7:e42617 pubmed publisher
    ..4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants. ..
  3. Pointer M, Kamilar J, Warmuth V, Chester S, Delsuc F, Mundy N, et al. RUNX2 tandem repeats and the evolution of facial length in placental mammals. BMC Evol Biol. 2012;12:103 pubmed publisher
    ..Thus, although RUNX2 might function as a 'tuning knob' modifying face length in carnivorans, this relationship is not conserved across mammals in general. ..
  4. Browne G, Nesbitt H, Ming L, Stein G, Lian J, McKeown S, et al. Bicalutamide-induced hypoxia potentiates RUNX2-mediated Bcl-2 expression resulting in apoptosis resistance. Br J Cancer. 2012;107:1714-21 pubmed publisher
  5. Li W, Xu S, Lin S, Zhao W. Overexpression of runt-related transcription factor-2 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer. J Biomed Biotechnol. 2012;2012:456534 pubmed publisher
    ..Our data suggest for the first time that RUNX2 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients. RUNX2 might be a novel prognostic marker of EOC. ..
  6. Matsushima S, Isogai N, Jacquet R, Lowder E, Tokui T, Landis W. The nature and role of periosteum in bone and cartilage regeneration. Cells Tissues Organs. 2011;194:320-5 pubmed publisher
    ..The appropriate periosteal choice for bone and cartilage tissue engineering and regeneration should be a function of its immediate application as well as other factors besides growth rate...
  7. Hsu Y, Huang M, Yang C, Hung J, Wu L, Kuo P. Lung tumor-associated osteoblast-derived bone morphogenetic protein-2 increased epithelial-to-mesenchymal transition of cancer by Runx2/Snail signaling pathway. J Biol Chem. 2011;286:37335-46 pubmed publisher
    ..Our findings provide novel evidence that inhibition of BMP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients. ..
  8. Baniwal S, Shah P, Shi Y, Haduong J, DeClerck Y, Gabet Y, et al. Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells. Osteoporos Int. 2012;23:1399-413 pubmed publisher
  9. Kim H, Min W, Jeong J, Kim S, Kim J, Kim S, et al. Combination of Runx2 and BMP2 increases conversion of human ligamentum flavum cells into osteoblastic cells. BMB Rep. 2011;44:446-51 pubmed
    ..Collectively, Runx2 plus BMP2 mediated efficient conversion of fibroblast-like LF cells into osteoblast- like cells, suggesting the possible use of these components for clinical applications such as spinal fusion...
  10. Koch F, Merkel C, Al Nawas B, Smeets R, Ziebart T, Walter C, et al. Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2. J Craniomaxillofac Surg. 2011;39:562-9 pubmed publisher
    ..The nitrogen-containing bisphosphonates appear to enhance bone density by stimulation of osteoblast differentiation. Non-nitrogen-containing bisphosphonates seem to have less influence on osteoblast differentiation. ..
  11. Byun M, Kim A, Hwang J, Sung M, Lee Y, Hwang B, et al. Phorbaketal A stimulates osteoblast differentiation through TAZ mediated Runx2 activation. FEBS Lett. 2012;586:1086-92 pubmed publisher
    ..Taken together, the results showed that phorbaketal A stimulates TAZ-mediated osteoblast differentiation through the activation of ERK. ..
  12. Zhu J, Shimizu E, Zhang X, Partridge N, Qin L. EGFR signaling suppresses osteoblast differentiation and inhibits expression of master osteoblastic transcription factors Runx2 and Osterix. J Cell Biochem. 2011;112:1749-60 pubmed publisher
  13. Singh S, Mak I, Cowan R, Turcotte R, Singh G, Ghert M. The role of TWIST as a regulator in giant cell tumor of bone. J Cell Biochem. 2011;112:2287-95 pubmed publisher
  14. Dy P, Wang W, Bhattaram P, Wang Q, Wang L, Ballock R, et al. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell. 2012;22:597-609 pubmed publisher
  15. Ohyama Y, Tanaka T, Shimizu T, Matsui H, Sato H, Koitabashi N, et al. Runx2/Smad3 complex negatively regulates TGF-?-induced connective tissue growth factor gene expression in vascular smooth muscle cells. J Atheroscler Thromb. 2012;19:23-35 pubmed
    ..Thus, the induction of Runx2 expression contributes to the phenotypic modulation of VSMCs, in which the TGF-?/Smad pathway plays a major role. ..
  16. Li Y, Ge C, Long J, Begun D, Rodriguez J, Goldstein S, et al. Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor. J Bone Miner Res. 2012;27:1263-74 pubmed publisher
    ..These findings establish ERK/MAPK-mediated phosphorylation of RUNX2 as a critical step in the response of preosteoblasts to dynamic loading and define a novel mechanism to explain how mechanical signals induce gene expression in bone. ..
  17. Bradley E, McGee Lawrence M, Westendorf J. Hdac-mediated control of endochondral and intramembranous ossification. Crit Rev Eukaryot Gene Expr. 2011;21:101-13 pubmed
    ..In this review, we summarize the roles of class I and class II Hdacs in chondrocytes and osteoblasts. The effects of small molecule Hdac inhibitors on the skeleton are also discussed. ..
  18. Mikasa M, Rokutanda S, Komori H, Ito K, Tsang Y, Date Y, et al. Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation. J Bone Miner Metab. 2011;29:291-9 pubmed publisher
    ..These findings indicate that Runx2 regulates chondrocyte maturation and proliferation at least partly through the induction of Tcf7. ..
  19. Liu Y, Zhao Y, Chen Y, Shi G, Yuan W. RUNX2 polymorphisms associated with OPLL and OLF in the Han population. Clin Orthop Relat Res. 2010;468:3333-41 pubmed publisher
  20. Liu J, Lengner C, Gaur T, Lou Y, Hussain S, Jones M, et al. Runx2 protein expression utilizes the Runx2 P1 promoter to establish osteoprogenitor cell number for normal bone formation. J Biol Chem. 2011;286:30057-70 pubmed publisher
    ..We conclude that selective utilization of the P1 and P2 promoters enables the precise spatiotemporal expression of Runx2 necessary for normal skeletogenesis and the maintenance of bone mass in the adult. ..
  21. Onodera Y, Miki Y, Suzuki T, Takagi K, Akahira J, Sakyu T, et al. Runx2 in human breast carcinoma: its potential roles in cancer progression. Cancer Sci. 2010;101:2670-5 pubmed publisher
    ..Results of our present study demonstrated that Runx2 plays very important roles in the progression of breast cancer, especially in those of ER-negative cases. ..
  22. Monroe D, Hawse J, Subramaniam M, Spelsberg T. Retinoblastoma binding protein-1 (RBP1) is a Runx2 coactivator and promotes osteoblastic differentiation. BMC Musculoskelet Disord. 2010;11:104 pubmed publisher
    ..As such, the effects of RBP1 on these processes are mediated through both regulation of Runx2 expression and transcriptional activity. ..
  23. Hie M, Tsukamoto I. Increased expression of the receptor for activation of NF-kappaB and decreased runt-related transcription factor 2 expression in bone of rats with streptozotocin-induced diabetes. Int J Mol Med. 2010;26:611-8 pubmed
    ..These suggested that short-term IDDM induced upregulation of osteoclastogenesis with an increase in RANK and downregulation of osteoblastogenesis with a decrease in Runx2 in bone. ..
  24. Blyth K, Vaillant F, Jenkins A, McDonald L, Pringle M, Huser C, et al. Runx2 in normal tissues and cancer cells: A developing story. Blood Cells Mol Dis. 2010;45:117-23 pubmed publisher
    ..Furthermore, we review the evidence that RUNX2 promotes neoplastic development in haematopoietic lineages and in advanced mammary and prostate cancer. ..
  25. Lee K, Jang W, Kim E, Oh S, Son H, Kim S, et al. Orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) protein negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation through suppressing runt-related gene 2 (Runx2) activity. J Biol Chem. 2012;287:18888-99 pubmed publisher
  26. Komori T. Signaling networks in RUNX2-dependent bone development. J Cell Biochem. 2011;112:750-5 pubmed publisher
    ..Thus, RUNX2 regulates osteoblast differentiation and chondrocyte maturation through the network with SP7 and with FGF, Wnt, and IHH signaling pathways during skeletal development. ..
  27. Baniwal S, Khalid O, Gabet Y, Shah R, Purcell D, Mav D, et al. Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis. Mol Cancer. 2010;9:258 pubmed publisher
    ..Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways. ..
  28. Bond S, Lau A, Penuela S, Sampaio A, Underhill T, Laird D, et al. Pannexin 3 is a novel target for Runx2, expressed by osteoblasts and mature growth plate chondrocytes. J Bone Miner Res. 2011;26:2911-22 pubmed publisher
    ..Taken together, our data suggests that Panx3 may serve an important role in bone development, and is a novel target for Runx2-dependent signaling...
  29. Wu T, Zhou H, Hong Y, Li J, Jiang X, Huang H. miR-30 family members negatively regulate osteoblast differentiation. J Biol Chem. 2012;287:7503-11 pubmed publisher
    ..Therefore, our study uncovered that miR-30 family members are key negative regulators of BMP-2-mediated osteogenic differentiation. ..
  30. Purcell D, Khalid O, Ou C, Little G, Frenkel B, Baniwal S, et al. Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression of transcription. J Cell Biochem. 2012;113:2406-14 pubmed publisher
    ..We conclude that a subset of cancer-related Runx2 target genes require recruitment of G9a for their expression, but do not depend on its histone methyltransferase activity. ..
  31. Tseng P, Hou S, Chen R, Peng H, Hsieh C, Kuo M, et al. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. J Bone Miner Res. 2011;26:2552-63 pubmed publisher
    ..Taken together, our results describe a novel mechanism of resveratrol in promoting osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. ..
  32. Laflamme C, Curt S, Rouabhia M. Epidermal growth factor and bone morphogenetic proteins upregulate osteoblast proliferation and osteoblastic markers and inhibit bone nodule formation. Arch Oral Biol. 2010;55:689-701 pubmed publisher
    ..This study demonstrated that EGF may act in the early phase to promote osteoblast growth and specific marker expression rather than the late phase involving cell differentiation/mineralization. ..
  33. Chimge N, Baniwal S, Little G, Chen Y, Kahn M, Tripathy D, et al. Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011;13:R127 pubmed publisher
    ..Unknown mechanisms in bone-seeking BCa allow high Runx2/SNAI2 expression despite high ER? level. ..
  34. Dingwall M, Marchildon F, Gunanayagam A, Louis C, Wiper Bergeron N. Retinoic acid-induced Smad3 expression is required for the induction of osteoblastogenesis of mesenchymal stem cells. Differentiation. 2011;82:57-65 pubmed publisher
    ..Taken together, these data indicate that Smad3 is an important mediator of RA activity during mesenchymal stem cell differentiation and is necessary for the stimulation of osteoblastogenesis. ..
  35. Ma H, Ming L, Ge B, Zhai Y, Song P, Xian C, et al. Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro. J Cell Biochem. 2011;112:916-23 pubmed publisher
  36. Leong D, Lim J, Goh X, Pratap J, Pereira B, Kwok H, et al. Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility. Breast Cancer Res. 2010;12:R89 pubmed publisher
    ..Our results support the emerging concept that the osteogenic transcription factor RUNX2 functions as a metastasis-related oncoprotein in non-osseous cancer cells. ..
  37. Shakibaei M, Buhrmann C, Mobasheri A. Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells. J Biol Chem. 2011;286:11492-505 pubmed publisher
  38. Mahalingam C, Datta T, Patil R, Kreider J, Bonfil R, Kirkwood K, et al. Mitogen-activated protein kinase phosphatase 1 regulates bone mass, osteoblast gene expression, and responsiveness to parathyroid hormone. J Endocrinol. 2011;211:145-56 pubmed publisher
    ..In conclusion, MKP1 is important for bone homeostasis, osteoblast differentiation and skeletal responsiveness to PTH. ..
  39. Dalle Carbonare L, Frigo A, Francia G, Davì M, Donatelli L, Stranieri C, et al. Runx2 mRNA expression in the tissue, serum, and circulating non-hematopoietic cells of patients with thyroid cancer. J Clin Endocrinol Metab. 2012;97:E1249-56 pubmed publisher
    ..05). This study can open up new research perspectives in the diagnosis and follow-up of PTC, even if further and larger cohort studies will be necessary to validate the Runx2 expression as biomarkers in thyroid cancer. ..
  40. Zhang H, Pan Y, Zheng L, Choe C, Lindgren B, Jensen E, et al. FOXO1 inhibits Runx2 transcriptional activity and prostate cancer cell migration and invasion. Cancer Res. 2011;71:3257-67 pubmed publisher
  41. Chimge N, Baniwal S, Luo J, Coetzee S, Khalid O, Berman B, et al. Opposing effects of Runx2 and estradiol on breast cancer cell proliferation: in vitro identification of reciprocally regulated gene signature related to clinical letrozole responsiveness. Clin Cancer Res. 2012;18:901-11 pubmed publisher
    ..Likely sensing the tension between them, letrozole responsiveness of a genomic node, positively regulated by estradiol and negatively regulated by Runx2 in vitro, best correlated with the clinical efficacy of letrozole treatment. ..
  42. He N, Xiao Z, Yin T, Stubbs J, Li L, Quarles L. Inducible expression of Runx2 results in multiorgan abnormalities in mice. J Cell Biochem. 2011;112:653-65 pubmed publisher
    ..Use of tissue specific Cre mice will allow this model to be used to conditionally and inducibly overexpress Runx2 in different tissues and provide a means to study the post-natal tissue- and cell context-dependent functions of Runx2...
  43. Ding M, Lu Y, Abbassi S, Li F, Li X, Song Y, et al. Targeting Runx2 expression in hypertrophic chondrocytes impairs endochondral ossification during early skeletal development. J Cell Physiol. 2012;227:3446-56 pubmed publisher
    ..This will change the local matrix environment, delay chondrocyte maturation, reduce apoptosis and matrix mineralization, and eventually, lead to impaired endochondral ossification. ..
  44. van der Deen M, Akech J, Lapointe D, Gupta S, Young D, Montecino M, et al. Genomic promoter occupancy of runt-related transcription factor RUNX2 in Osteosarcoma cells identifies genes involved in cell adhesion and motility. J Biol Chem. 2012;287:4503-17 pubmed publisher
    ..Our results reveal that siRNA depletion of RUNX2, PTK2, or TLN1 diminishes motility of U2OS osteosarcoma cells. Thus, RUNX2 binding to diverse gene loci may support the biological properties of osteosarcoma cells. ..
  45. Nishikawa K, Nakashima T, Takeda S, Isogai M, Hamada M, Kimura A, et al. Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation. J Clin Invest. 2010;120:3455-65 pubmed publisher
    ..This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases...
  46. Jang W, Kim E, Kim D, Ryoo H, Lee K, Kim S, et al. BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. J Biol Chem. 2012;287:905-15 pubmed publisher
    ..Overall, these results suggest that BMP2 induces osteoblast differentiation through Runx2-dependent ATF6 expression, which directly regulates Oc transcription. ..
  47. Baniwal S, Little G, Chimge N, Frenkel B. Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation. J Cell Physiol. 2012;227:2276-82 pubmed publisher
    ..Our data suggest that Runx2 controls a positive feedback loop between androgen signaling and PIP, and pharmacological inhibition of PIP may be useful to treat PIP positive tumors. ..
  48. Wen J, Tao R, Ni L, Duan Q, Lu Q. Immunolocalization and expression of Runx2 in tertiary dentinogenesis. Hybridoma (Larchmt). 2010;29:195-9 pubmed publisher
    ..Taken together, the expression of Runx2 has temporal and spatial specificity during different phases in rat tertiary dentinogenesis...
  49. Speer M, Li X, Hiremath P, Giachelli C. Runx2/Cbfa1, but not loss of myocardin, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis. J Cell Biochem. 2010;110:935-47 pubmed publisher
    ..On the other hand, Runx2/Cbfa1 was found to be a decisive factor identified in the process...
  50. Welting T, Caron M, Emans P, Janssen M, Sanen K, Coolsen M, et al. Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification. Eur Cell Mater. 2011;22:420-36; discussion 436-7 pubmed
  51. Zhang Y, Xie R, Croce C, Stein J, Lian J, Van Wijnen A, et al. A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci U S A. 2011;108:9863-8 pubmed publisher
    ..These findings demonstrate that osteoblastogenesis is limited by an elaborate network of functionally tested miRNAs that directly target the osteogenic master regulator Runx2. ..
  52. Goloudina A, Tanoue K, Hammann A, Fourmaux E, Le Guezennec X, Bulavin D, et al. Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. Proc Natl Acad Sci U S A. 2012;109:E68-75 pubmed publisher
    ..Thus, Wip1 phosphatase promotes apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. ..
  53. Jeong J, Choi J. Interrelationship of Runx2 and estrogen pathway in skeletal tissues. BMB Rep. 2011;44:613-8 pubmed publisher
    ..In this review, a possible functional link between Runx2 and estrogen synthesis pathway in skeletal tissues will be discusses as well as the biological significance of this interaction. ..