A twist code determines the onset of osteoblast differentiation
- PMID: 15030764
- DOI: 10.1016/s1534-5807(04)00058-9
A twist code determines the onset of osteoblast differentiation
Abstract
Runx2 is necessary and sufficient for osteoblast differentiation, yet its expression precedes the appearance of osteoblasts by 4 days. Here we show that Twist proteins transiently inhibit Runx2 function during skeletogenesis. Twist-1 and -2 are expressed in Runx2-expressing cells throughout the skeleton early during development, and osteoblast-specific gene expression occurs only after their expression decreases. Double heterozygotes for Twist-1 and Runx2 deletion have none of the skull abnormalities observed in Runx2(+/-) mice, a Twist-2 null background rescues the clavicle phenotype of Runx2(+/-) mice, and Twist-1 or -2 deficiency leads to premature osteoblast differentiation. Furthermore, Twist-1 overexpression inhibits osteoblast differentiation without affecting Runx2 expression. Twist proteins' antiosteogenic function is mediated by a novel domain, the Twist box, which interacts with the Runx2 DNA binding domain to inhibit its function. In vivo mutagenesis confirms the antiosteogenic function of the Twist box. Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation.
Comment in
-
Twist genes regulate Runx2 and bone formation.Dev Cell. 2004 Mar;6(3):317-8. doi: 10.1016/s1534-5807(04)00069-3. Dev Cell. 2004. PMID: 15030754
Similar articles
-
Twist genes regulate Runx2 and bone formation.Dev Cell. 2004 Mar;6(3):317-8. doi: 10.1016/s1534-5807(04)00069-3. Dev Cell. 2004. PMID: 15030754
-
Core-binding factor beta interacts with Runx2 and is required for skeletal development.Nat Genet. 2002 Dec;32(4):633-8. doi: 10.1038/ng1015. Epub 2002 Nov 18. Nat Genet. 2002. PMID: 12434152
-
TWIST inactivation reduces CBFA1/RUNX2 expression and DNA binding to the osteocalcin promoter in osteoblasts.Biochem Biophys Res Commun. 2002 Sep 27;297(3):641-4. doi: 10.1016/s0006-291x(02)02260-x. Biochem Biophys Res Commun. 2002. PMID: 12270142
-
Regulatory mechanisms of osteoblast and osteoclast differentiation.Oral Dis. 2002 May;8(3):147-59. doi: 10.1034/j.1601-0825.2002.01829.x. Oral Dis. 2002. PMID: 12108759 Review.
-
Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors.Crit Rev Eukaryot Gene Expr. 2004;14(1-2):1-41. Crit Rev Eukaryot Gene Expr. 2004. PMID: 15104525 Review.
Cited by
-
An evolutionarily conserved DNA architecture determines target specificity of the TWIST family bHLH transcription factors.Genes Dev. 2015 Mar 15;29(6):603-16. doi: 10.1101/gad.242842.114. Epub 2015 Mar 11. Genes Dev. 2015. PMID: 25762439 Free PMC article.
-
Ribosome biogenesis controls cranial suture MSC fate via the complement pathway in mouse and human iPSC models.Stem Cell Reports. 2023 Dec 12;18(12):2370-2385. doi: 10.1016/j.stemcr.2023.10.015. Epub 2023 Nov 16. Stem Cell Reports. 2023. PMID: 37977145 Free PMC article.
-
Bone marrow mesenchymal stem cells of the intrauterine growth-restricted rat offspring exhibit enhanced adipogenic phenotype.Int J Obes (Lond). 2016 Nov;40(11):1768-1775. doi: 10.1038/ijo.2016.157. Epub 2016 Sep 7. Int J Obes (Lond). 2016. PMID: 27599633 Free PMC article.
-
Effect of lyso-phosphatidylcholine and Schnurri-3 on osteogenic transdifferentiation of vascular smooth muscle cells to calcifying vascular cells in 3D culture.Biochim Biophys Acta. 2013 Jun;1830(6):3828-34. doi: 10.1016/j.bbagen.2013.02.015. Epub 2013 Mar 14. Biochim Biophys Acta. 2013. PMID: 23500015 Free PMC article. Clinical Trial.
-
miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2.J Cell Biol. 2012 May 14;197(4):509-21. doi: 10.1083/jcb.201201057. Epub 2012 May 7. J Cell Biol. 2012. PMID: 22564414 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
