RUNX2 regulates bone development

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Homo sapiens
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RUNX2 is required for the development of both intramembraneous and endochondral bones through regulation of osteoblast differentiation and chondrocyte maturation, respectively. In its absence, intramembraneous ossification is blocked while endochondral ossification is arrested at the cartilaginous stage (Otto et al. 1997, Komori et al. 1997). In mice and humans, RUNX2 haploinsufficiency causes Cleidocranial dysplasia, a generalized bone disorder (Otto et al. 1997, Lee et al. 1997).
RUNX2 stimulates transcription of most of the genes constituting the bone extracellular matrix and of BGLAP gene, which encodes Osteocalcin, a bone-derived hormone controlling glucose metabolism, male fertility and cognition (Ducy et al. 1997).
RUNX2 promotes chondrocyte maturation by stimulating transcription of the IHH gene, encoding Indian hedgehog (Takeda et al. 2001, Yoshida et al. 2004).
In response to BMP2 signaling, RUNX2 forms a complex with SMAD1:SMAD4 heterotrimer in the nucleus and stimulates transcription of SMAD6 (Wang et al. 2007).
RBM14, a negative regulator of RUNX2 transcriptional activity, is frequently overexpressed in osteosarcoma (Li et al. 2009).

Literature References
PubMed ID Title Journal Year
11230154 Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice

Owen, MJ, Takeda, S, Karsenty, G, Ducy, P, Bonnamy, JP

Genes Dev. 2001
9182762 Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation

Geoffroy, V, Ridall, AL, Karsenty, G, Ducy, P, Zhang, R

Cell 1997
9182764 Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development

Rosewell, IR, Owen, MJ, Mundlos, S, Otto, F, Thornell, AP, Stamp, GW, Beddington, RS, Selby, PB, Gilmour, KC, Denzel, A, Olsen, BR, Crompton, T

Cell 1997
19585539 Co-activator activator (CoAA) prevents the transcriptional activity of Runt domain transcription factors

Gopalakrishnan, R, Jensen, ED, Westendorf, JJ, Li, X, Hoeppner, LH

J. Cell. Biochem. 2009
9207800 Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia

Geoffroy, V, Hecht, J, Karsenty, G, Pastore, L, Ducy, P, Zhou, L, Thirunavukkarasu, K, Baldini, A, Lee, B

Nat. Genet. 1997
9182763 Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts

Yagi, H, Gao, YH, Deguchi, K, Kishimoto, T, Okamoto, R, Sato, M, Bronson, RT, Inada, M, Nomura, S, Kitamura, Y, Yoshiki, S, Yamaguchi, A, Komori, T, Shimizu, Y, Sasaki, K

Cell 1997
15107406 Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog

Ito, Y, Fujita, T, Komori, T, Inoue, K, Takada, K, Yoshida, CA, Furuichi, T, Yamamoto, H, Zanma, A, Ito, K, Yamana, K

Genes Dev. 2004
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