RUNX2 regulates chondrocyte maturation

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Homo sapiens
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In addition to regulating osteoblast differentiation, RUNX2 regulates skeletal development by regulating maturation of chondrocytes (Takeda et al. 2001). Chondrocyte maturation happens during the process of endochondral ossification. Expression of the parathyroid hormone receptor (PTHR1) and Indian hedgehog (IHH) are hallmarks of chondrocyte maturation. Mice that are double knockouts for Runx2 and Runx3 show a complete absence of chondrocyte maturation and, hence, aberrant limb growth. Based on mouse studies, RUNX2 directly regulates transcription of the IHH gene. RUNX2 binding sites in the IHH gene promoter are conserved in humans (Yoshida et al. 2004). Also based on mouse studies, RUNX2 positively regulates transcription of NELL1 (neural EGFL-like 1), a key functional mediator of chondrogenesis, but direct binding of RUNX2 to the NELL1 gene locus has not been demonstrated (Li et al. 2017). Runx2 binding sites exist in the enhancer of the mouse Col10a1 gene, encoding type X collagen, a marker of hypertrophic chondrocytes, which is critical for endochondral bone formation. While Runx2 binding is required, it is not sufficient to trigger Col10a1 transcription (Gu et al. 2014).

Literature References
PubMed ID Title Journal Year
25321476 Identification and characterization of the novel Col10a1 regulatory mechanism during chondrocyte hypertrophic differentiation

Gu, J, Wang, Q, Lei, G, Lu, Y, Borgia, JA, Li, N, Qiao, L, Li, F, Zheng, Q, Deng, Y

Cell Death Dis 2014
28302495 Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation

Zhou, Y, Li, C, Chen, E, Chen, X, Soo, C, Zheng, Z, Jiang, J, Culiat, CT, Qiao, Y, Ting, K, Zhang, X, Lee, KS

Am. J. Pathol. 2017
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
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
Cross References
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