RUNX2 regulates chondrocyte maturation

Summary
Organism
Homo sapiens (human)
Reactome
R-HSA-8941284
PubChem
R-HSA-8941284
Description
  • 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).
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
Displaying all 4 entries
UniProt ID Protein Name Gene Symbol Pathway Viewer
P10070 Zinc finger protein GLI2
  • GLI2
  • THP
view
P56524 Histone deacetylase 4
  • HDAC4
  • KIAA0288
view
Q13951 Core-binding factor subunit beta
  • CBFB
view
Q14623 Indian hedgehog protein
  • IHH
view

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Acknowledgements

Supported by JST NBDC Grant Number JPMJND2204

Partly supported by NIH Common Fund Grant #1U01GM125267-01


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