Epigenetic regulation of osteogenic potential in mesenchymal stem cells derived from periodontal ligament

• Grant number: 17/07944-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2018
• End date: September 30, 2020
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Agreement: University of Birmingham
• Principal Investigator: Denise Carleto Andia
• Grantee: Denise Carleto Andia
• Principal researcher abroad: Malgorzata Wiench
• Institution abroad: University of Birmingham, England
• Host Institution: Instituto de Ciências da Saúde (ICS). Universidade Paulista (UNIP). São Paulo , SP, Brazil
• Associated researchers: Ben A. Scheven ; Karina Gonzales Silvério Ruiz

Abstract

Multipotent periodontal ligament stem cells (PDLSCs) like other mesenchymal stem cells (MSCs) can give rise to bone, cartilage and fat tissues. They are relatively easily obtained during a third molar extraction and have been recently shown to have both good osteogenic potential and proliferation capacity. Therefore, they are promising candidates not only for periodontal regeneration but also for regenerative therapies in a broad range of bone diseases. However, the molecular mechanisms underlying osteogenic differentiation of PDLSCs are still not well understood with very limited information available regarding their epigenetic background and regulation. Such information is indispensable in order to safely apply PDLSCs in human clinical trials. In this project we aim to provide a substantial amount of data that will help to fill in the gap in our understanding of osteogenesis and mesenchymal stem cell differentiation. Firstly, the genome wide changes in DNA methylation and hydroxymethylation, chromatin accessibility and bone-specific transcription factor binding will be studied in PDLSCs during the process of osteogenic differentiation in order to appreciate their effect on bone-specific gene transcription. Secondly, the PDLSC populations with high and low osteogenic potential will be compared aiming to select potential epigenetic markers of preferential differentiation towards osteoblasts. And finally, in the second part of the project we will investigate the possibility of RE1-transcription factor (REST) being a novel regulator of osteogenic differentiation, the action of which could be modified by a plant polyphenol resveratrol. With its focus on tissue regeneration therapies the project aligns very well with the interest of both the School of Dentistry, Paulista University and the School of Dentistry, University of Birmingham and we expect it to develop into a long-lasting collaboration attracting other fellow researchers and postgraduate students. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ASSIS, RAHYZA I. F.; SCHMIDT, ARTHUR G.; RACCA, FRANCESCA; DA SILVA, RODRIGO A.; ZAMBUZZI, WILLIAM F.; SILVERIO, KARINA G.; NOCITI, FRANCISCO H.; PECORARI, VANESSA G.; WIENCH, MALGORZATA; ANDIA, DENISE C.. DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells. DNA AND CELL BIOLOGY, v. 40, n. 5, MAR 2021. (13/09650-8, 15/02160-0, 17/07944-5)

ASSIS, RAHYZA I. F.; FELTRAN, GEORGIA DA S.; SALOMAO SILVA, MARIA EDUARDA; DO ROSARIO PALMA, IASMIN CAROLINE; ROVAI, EMANUEL SILVA; DE MIRANDA, TAIS BROWNE; FERREIRA, MARCEL RODRIGUES; ZAMBUZZI, WILLIAN F.; BIRBRAIR, ALEXANDER; ANDIA, DENISE C.; et al. Non-coding RNAs repressive role in post-transcriptional processing of RUNX2 during the acquisition of the osteogenic phenotype of periodontal ligament mesenchymal stem cells. Developmental Biology, v. 470, p. 37-48, FEB 2021. (17/07944-5, 17/12158-9)

ASSIS, RAHYZA I. F.; RACCA, FRANCESCA; FERREIRA, ROGERIO S.; RUIZ, KARINA G. S.; DA SILVA, RODRIGO A.; CLOKIE, SAMUEL J. H.; WIENCH, MALGORZATA; ANDIA, DENISE C.. Osteogenic Commitment of Human Periodontal Ligament Cells Is Predetermined by Methylation, Chromatin Accessibility and Expression of Key Transcription Factors. CELLS, v. 11, n. 7, p. 20-pg., 2022-04-01. (19/01727-8, 17/07944-5, 17/12158-9)

FERREIRA, ROGERIO S.; ASSIS, RAHYZA I. F.; RACCA, FRANCESCA; BONTEMPI, ANA CAROLINA; DA SILVA, RODRIGO A.; WIENCH, MALGORZATA; ANDIA, DENISE C.. Analyzes In Silico Indicate the lncRNAs MIR31HG and LINC00939 as Possible Epigenetic Inhibitors of the Osteogenic Differentiation in PDLCs. GENES, v. 14, n. 8, p. 21-pg., 2023-08-01. (17/07944-5)