Signaling Networks in RUNX2-dependent Bone Development

J Cell Biochem. 2011 Mar;112(3):750-5. doi: 10.1002/jcb.22994.


RUNX2 is an essential transcription factor for osteoblast differentiation and chondrocyte maturation. SP7, another transcription factor, is required for osteoblast differentiation. Major signaling pathways, including FGF, Wnt, and IHH, also play important roles in skeletal development. RUNX2 regulates Sp7 expression at an early stage of osteoblast differentiation. FGF2 upregulates Runx2 expression and activates RUNX2, and gain-of-function mutations of FGFRs cause craniosynostosis and limb defect with upregulation of Runx2 expression. Wnt signaling upregulates Runx2 expression and activates RUNX2, and RUNX2 induces Tcf7 expression. IHH is required for Runx2 expression in osteoprogenitor cells during endochondral bone development, and RUNX2 directly regulates Ihh expression in chondrocytes. Thus, RUNX2 regulates osteoblast differentiation and chondrocyte maturation through the network with SP7 and with FGF, Wnt, and IHH signaling pathways during skeletal development.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Development*
  • Cell Differentiation
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Hedgehog Proteins / metabolism
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction*
  • Sp7 Transcription Factor
  • Transcription Factors / metabolism
  • Wnt Proteins / metabolism


  • Core Binding Factor Alpha 1 Subunit
  • Hedgehog Proteins
  • RUNX2 protein, human
  • Receptors, Fibroblast Growth Factor
  • Sp7 Transcription Factor
  • Sp7 protein, human
  • Transcription Factors
  • Wnt Proteins