Features: Volume 112, Number 3

• Book ID: 102303826
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 109 KB
• Volume: 112
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22808

✦ Synopsis

RUNX2 plays important roles in bone development by regulating the differentiation of osteoblasts and chondrocytes. The major issue is how RUNX2 regulates differentiation of the two different lineages at an appropriate time and space during bone development. Komori proposes that reciprocal regulations among RUNX2 and SP7 (another essential transcription factor for osteoblast differentiation), and major signaling pathways, (including FGF, Wnt, and IHH), form a crucial signaling network for the regulation of osteoblast and chondrocyte differentiation. RUNX2 and canonical Wnt signaling are required for Sp7 expression at an early stage of osteoblast differentiation. FGF2 upregulates Runx2 expression and activates RUNX2, and Runx2 expression is upregulated in gain-of-function mutations of FGFRs. Canonical Wnt signaling upregulates Runx2 expression and activates RUNX2, and RUNX2 induces Tcf7 expression. Runx2 also interacts with TCF/LEF transcription factors and regulates transcription. In the process of endochondral ossifi cation, reciprocal regulation of RUNX2 and IHH coordinates chondrocyte maturation and proliferation in the growth plates and regulates osteoblast differentiation at the perichondrium. Komori indicates that the key molecules and signaling pathways control the process of bone development by regulating each other and that further elucidation of reciprocal regulations would reveal why RUNX2 plays critical roles in both osteoblasts and chondrocytes.