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 <i>RUNX2</i> gene have been identified in most CCD patients. Transcrip...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10336 |
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| author | Luca Dalle Carbonare Franco Antoniazzi Alberto Gandini Silvia Orsi Jessica Bertacco Veronica Li Vigni Arianna Minoia Francesca Griggio Massimiliano Perduca Monica Mottes Maria Teresa Valenti |
| author_facet | Luca Dalle Carbonare Franco Antoniazzi Alberto Gandini Silvia Orsi Jessica Bertacco Veronica Li Vigni Arianna Minoia Francesca Griggio Massimiliano Perduca Monica Mottes Maria Teresa Valenti |
| author_sort | Luca Dalle Carbonare |
| collection | DOAJ |
| description | 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 <i>RUNX2</i> gene have been identified in most CCD patients. Transcription factor <i>RUNX2</i>, 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 <i>RUNX2</i> mutations in CCD patients, we investigated <i>RUNX2</i> gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how <i>RUNX2</i> 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, <i>RUNX2</i> mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of <i>RUNX2</i> mutations in CCD patients and suggests that an in-depth analysis of the <i>RUNX2</i>-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:19Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dea613e50ad145a2b4e0d170b74a39802023-11-22T16:08:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191033610.3390/ijms221910336Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 ExpressionLuca Dalle Carbonare0Franco Antoniazzi1Alberto Gandini2Silvia Orsi3Jessica Bertacco4Veronica Li Vigni5Arianna Minoia6Francesca Griggio7Massimiliano Perduca8Monica Mottes9Maria Teresa Valenti10Department of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37100 Verona, ItalyDepartment of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyCentro Piattaforme Tecnologiche, University of Verona, 37100 Verona, ItalyBiocrystallography Lab, Department of Biotechnology, University of Verona, 37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyCleidocranial 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 <i>RUNX2</i> gene have been identified in most CCD patients. Transcription factor <i>RUNX2</i>, 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 <i>RUNX2</i> mutations in CCD patients, we investigated <i>RUNX2</i> gene expression and the osteogenic potential of two CCD patients’ cells. In addition, with the aim to better understand how <i>RUNX2</i> 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, <i>RUNX2</i> mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of <i>RUNX2</i> mutations in CCD patients and suggests that an in-depth analysis of the <i>RUNX2</i>-associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects.https://www.mdpi.com/1422-0067/22/19/10336cleidocranial dysplasiaboneosteogenic differentiationRUNX2 |
| spellingShingle | Luca Dalle Carbonare Franco Antoniazzi Alberto Gandini Silvia Orsi Jessica Bertacco Veronica Li Vigni Arianna Minoia Francesca Griggio Massimiliano Perduca Monica Mottes Maria Teresa Valenti Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression International Journal of Molecular Sciences cleidocranial dysplasia bone osteogenic differentiation RUNX2 |
| title | Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression |
| title_full | Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression |
| title_fullStr | Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression |
| title_full_unstemmed | Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression |
| title_short | Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression |
| title_sort | two novel c terminus runx2 mutations in two cleidocranial dysplasia ccd patients impairing p53 expression |
| topic | cleidocranial dysplasia bone osteogenic differentiation RUNX2 |
| url | https://www.mdpi.com/1422-0067/22/19/10336 |
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