Regulation of bone development and extracellular matrix protein genes by RUNX2

By T. Komori. Cell and Tissue Research, 2009

787 citations recorded by the source corpus.

RUNX2 is a multifunctional transcription factor that controls skeletal development by regulating the differentiation of chondrocytes and osteoblasts and the expression of many extracellular matrix protein genes during chondrocyte and osteoblast differentiation. This transcription factor plays a major role at the late stage of chondrocyte differentiation: it is required for chondrocyte maturation and regulates Col10a1 expression in hypertrophic chondrocytes and the expression of Spp1, Ibsp, and Mmp13 in terminal hypertrophic chondrocytes. It is essential for the commitment of pluripotent mesenchymal cells to the osteoblast lineage. During osteoblast differentiation, RUNX2 upregulates the expression of bone matrix protein genes including Col1a1, Spp1, Ibsp, Bglap, and Fn1 in vitro and activates many promoters including those of Col1a1, Col1a2, Spp1, Bglap, and Mmp13. However, overexpression of Runx2 inhibits osteoblast maturation and reduces Col1a1 and Bglap expression. The inhibition of RUNX2 in mature osteoblasts does not reduce the expression of Col1a1 and Bglap in mice. Thus, RUNX2 directs pluripotent mesenchymal cells to the osteoblast lineage, triggers the expression of major bone matrix protein genes, and keeps the osteoblasts in an immature stage, but does not play a major role in the maintenance of the expression of Col1a1 or Bglap in mature osteoblasts. During bone development, RUNX2 induces osteoblast differentiation and increases the number of immature osteoblasts, which form immature bone, whereas Runx2 expression has to be downregulated for differentiation into mature osteoblasts, which form mature bone. During dentinogenesis, Runx2 expression is downregulated, and RUNX2 inhibits the terminal differentiation of odontoblasts.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/b72e32c9be909f9c2aea7c29f8ade03425c1eb5d

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Citations in the corpus

• Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? (2016, background): “In addition, Runx2 has been shown to be required for the induction of major bone matrix genes in immature osteoblasts, while unnecessary for themaintenance of these genes in mature osteoblasts.(91) Indeed, one recent study has demonstrated that the feedforward regulation between Runx2 and Glut1 (a g”
• The Regulation of Differentiation in Mesenchymal Stem Cells (2010, neutral): “…intervening in osteogenic differentiation are CBFA-1/Runx2 and Osterix (Osx), known to be required for bone formation during development (Schroeder et al. , 2005; Komori, 2010), whereas Sox9 is a transcription factor required for cartilage formation (Akiyama et al. , 2004; Quintana et al. , 2009).”
• Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness (2018, background): “The relative expression of Runx2 and Sox9 subsequently determines osteogenic or chondrogenic lineage, with Runx2 driving the osteogenic phenotype, whilst Sox9 binds to Runx2 and represses its actions.30 In the osteogenic phenotype, the Runx2 transcription factor in turn binds to downstream genes reg”