Expression of RUNX2 and its signaling partners TCF7, FGFR1/2 in cleidocranial dysplasia

• Authors: Elżbieta Pawłowska , Katarzyna Wójcik , Ewelina Synowiec , Joanna Szczepańska , Janusz Błasiak
• Languages of publication: EN

Abstracts

EN

RUNX2 is a member of the PEBP2/CBF transcription factors family controlling the expression of genes whose products are essential for bone formation. Mutations in the RUNX2 gene may be associated with cleidocranial dysplasia (CCD), a rare skeletal disease characterized by stature aberrations, delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and multiple dental abnormalities. As RUNX2 is involved in many signaling pathways, we hypothesize that CCD may be associated with their changes. We determined the expression of RUNX2 and its signaling partners TCF7, involved in canonical Wnt signaling, and fibroblast growth factor receptors, FGFR1 and FGFR2 in periodontum of CCD patients and control individuals. We did not observe any differences between the level of RUNX2, TCF7 and FGFR1/2 mRNA, determined by real-time PCR, in CDD patients and controls. Therefore, RUNX2 signaling pathways with their partners TCF7 and FGFR1/2 may not be involved in CCD pathogenesis.

Keywords

EN

RUNX2; Wnt signaling; TCF7; fibroblast growth factor signaling; FGFR1; FGFR2

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2015
• Volume: 62
• Issue: 1
• Pages: 123-126

Dates

published

2015

received

2014-07-18

revised

2014-11-12

accepted

2014-12-17

online

2015-03-05

Contributors

author

Elżbieta Pawłowska

• Department of Orthodontics, Medical University of Lodz, Łódź, Poland

author

Katarzyna Wójcik

• Faculty of Biology and Environmental Protection, Department of Molecular Genetics, University of Lodz, Łódź, Poland

author

Ewelina Synowiec

• Faculty of Biology and Environmental Protection, Department of Molecular Genetics, University of Lodz, Łódź, Poland

author

Joanna Szczepańska

• Department of Pediatric Dentistry, Medical University of Lodz, Łódź, Poland

author

Janusz Błasiak

• Faculty of Biology and Environmental Protection, Department of Molecular Genetics, University of Lodz, Łódź, Poland

References

• Aberg T, Cavender A, Gaikwad JS, Bronckers AL, Wang X, Waltimo-Siren J, Thesleff I, D'Souza RN (2004) Phenotypic changes in dentition of Runx2 homozygote-null mutant mice. J Histochem Cytochem 52: 131-139.
• Baumert U, Golan I, Redlich M, Aknin JJ, Muessig D (2005) Cleidocranial dysplasia: molecular genetic analysis and phenotypic-based description of a Middle European patient group. Am J Med Genet A 139A: 78-85.
• Bergwitz C, Prochnau A, Mayr B, Kramer FJ, Rittierodt M, Berten HL, Hausamen JE, Brabant G (2001) Identification of novel CBFA1/RUNX2 mutations causingcleidocranial dysplasia. J Inherit Metab Dis 24: 648-656.
• Chang JY, Wang C, Liu J, Huang Y, Jin C, Yang C, Hai B, Liu F, D'Souza RN, McKeehan WL, Wang F (2013) Fibroblast growth factor signaling is essential for self-renewal of dental epithelial stem cells. J Biol Chem 288: 28952-28961.
• Deng ZL, Sharff KA, Tang N, Song WX, Luo J, Luo X, Chen J, Bennett E, Reid R, Manning D, Xue A, Montag AG, Luu HH, Haydon RC, He TC (2008) Regulation of osteogenic differentiation during skeletal development. Front Biosci 13: 2001-2021.
• D'Souza RN, Aberg T, Gaikwad J, Cavender A, Owen M, Karsenty G, Thesleff I (1999) Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development 126: 2911-2920.
• Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89: 747-754.
• Franceschi RT, Xiao G, Jiang D, Gopalakrishnan R, Yang S, Reith E (2003) Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation. Connect Tissue Res 44: 109-116.
• Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280: 33132-33140.
• Goetz R, Mohammadi M (2013) Exploring mechanisms of FGF signalling through the lens of structural biology. Nat Rev Mol Cell Biol 14: 166-180.
• Jensen BL, Kreiborg S (1990) Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med 19: 89-93.
• Jonason JH, Xiao G, Zhang M, Xing L, Chen D (2009) Post-translational Regulation of Runx2 in Bone and Cartilage. J Dent Res 88: 693-703.
• Kim HJ, Kim JH, Bae SC, Choi JY, Kim HJ, Ryoo HM (2003) The protein kinase C pathway plays a central role in the fibroblast growth factor-stimulated expression and transactivation activity of Runx2. J Biol Chem 278: 319-326.
• Kim BG, Kim HJ, Park HJ, Kim YJ, Yoon WJ, Lee SJ, Ryoo HM, Cho JY (2006) Runx2 phosphorylation induced by fibroblast growth factor-2/protein kinase C pathways. Proteomics 6: 1166-1174.
• Komori T (2011) Signaling networks in RUNX2-dependent bone development. J Cell Biochem 112: 750-755.
• Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G (1997) Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet 16: 307-310.
• Li CY, Prochazka J, Goodwin AF, Klein OD (2014) Fibroblast growth factor signaling in mammalian tooth development. Odontology 102: 1-13.
• Lu Y, Li Y, Cavender AC, Wang S, Mansukhani A, D'Souza RN (2012) Molecular studies on the roles of Runx2 and Twist1 in regulating FGF signaling. Dev Dyn 241: 1708-1715.
• Mikasa M, Rokutanda S, Komori H, Ito K, Tsang YS, Date Y, Yoshida CA, Komori T (2011) Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation. J Bone Miner Metab 29: 291-299.
• Morriss-Kay GM, Wilkie AO (2005) Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies. J Anat 207: 637-653.
• Nishimura R, Hata K, Matsubara T, Wakabayashi M, Yoneda T (2012) Regulation of bone and cartilage development by network between BMP signalling and transcription factors J Biochem 151: 247-254.
• Rice DP, Rice R, Thesleff I (2003) Molecular mechanisms in calvarial bone and suture development, and their relation to craniosynostosis. Eur J Orthod 25: 139-148.
• Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3: 1101-1118.
• Shui C, Spelsberg TC, Riggs BL, Khosla S (2003) Changes in Runx2/Cbfa1 expression and activity during osteoblastic differentiation of human bone marrow stromal cells. J Bone Miner Res 18: 213-221.
• Silvério KG, Davidson KC, James RG, Adams AM, Foster BL, Nociti FH Jr, Somerman MJ, Moon RT (2012) Wnt/β-catenin pathway regulates bone morphogenetic protein (BMP2)-mediated differentiation of dental follicle cells. J Periodontal Res 47: 309-19.
• Wang X, Manner PA, Horner A, Shum L, Tuan RS, Nuckolls GH (2004) Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis Cartilage 12: 963-973.
• Wuelling M, Vortkamp A (2011) Chondrocyte proliferation and differentiation. Endocr Dev 21: 1-11.
• Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G, Franceschi RT (2000) MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem 275: 4453-4459.
• Zhang C, Zheng S, Wang Y, Zhao Y, Zhu J, Ge L (2010) Mutational analysis of RUNX2 gene in Chinese patients with cleidocranial dysplasia. Mutagenesis 25: 589-594.
• Ziros PG, Gil AP, Georgakopoulos T, Habeos I, Kletsas D, Basdra EK, Papavassiliou AG (2002) The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem 277: 23934-23941.