Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression.
Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the RUNX2 gene have been identified in most CCD patients. Transcription factor RUNX2, the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of RUNX2 mutations in CCD patients, we investigated RUNX2 gene expression and the osteogenic potential of two CCD patients' cells. In addition, with the aim to better understand how RUNX2 mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, RUNX2 mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of RUNX2 mutations in CCD patients and suggests that an in-depth analysis of the RUNX2-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects.
['Dalle Carbonare|Luca|L|0000-0003-3263-6671', 'Antoniazzi|Franco|F|', 'Gandini|Alberto|A|', 'Orsi|Silvia|S|', 'Bertacco|Jessica|J|', 'Li Vigni|Veronica|V|', 'Minoia|Arianna|A|0000-0003-4610-1168', 'Griggio|Francesca|F|', 'Perduca|Massimiliano|M|0000-0001-8291-0523', 'Mottes|Monica|M|0000-0002-7390-2246', 'Valenti|Maria Teresa|MT|0000-0003-1166-8033']
D000595:Amino Acid Sequence D001483:Base Sequence D002454:Cell Differentiation D002648:Child D002973:Cleidocranial Dysplasia D050659:Core Binding Factor Alpha 1 Subunit D005260:Female D053263:Gene Regulatory Networks D006801:Humans D008297:Male D009154:Mutation D010006:Osteoblasts D010012:Osteogenesis D016159:Tumor Suppressor Protein p53
RUNX2 cleidocranial dysplasia osteogenic differentiation bone