Participation of the lncRNA MIR31HG on the epigenetic regulation of mesenchymal stem cells during osteoblastic differentiation and in the interaction with titanium

• Grant number: 22/04770-4
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2023 - April 30, 2025
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Denise Carleto Andia
• Grantee: Denise Carleto Andia
• Host Institution: Vice-Reitoria de Pesquisa e Pós-Graduação. Universidade Paulista (UNIP). São Paulo , SP, Brazil
• Associated researchers: Márcio Mateus Beloti ; Rodrigo Augusto da Silva

Abstract

Despite the high occurrence of bone diseases and defects, the epigenetic background related to bone biology still represents a challenge. The results we have published so far highlight the individual epigenetic and transcriptional landscapes as strongly related to the acquisition of a specific osteogenic phenotype while the unpublished data recently obtained in our lab suggest the involvement of long non-coding RNAs (lncRNAs). lncRNAs have emerged as promising tools of osteogenesis-related gene modulation and participate in epigenetic regulation by binding to chromatin regulatory proteins. Here we aim to use a challenging model (mesenchymal cells from periodontal ligament presenting low potential for extracellular matrix formation, l-PDLCs) and cutting-edge methodologies to evaluate the role of a novel lncRNA on osteogenesis. The Bioinformatic analysis of epigenomic data from the previous Grant (FAPESP/University of Birmingham, UK) pointed us to the lncRNA MIR31HG as a strong target to be further investigated on bone biology. In the Part 1, the goal is to investigate the role of the lncRNA MIR31HG on the epigenetic regulation of extracellular mineralized matrix formation, in l-PDLCs immortalized and edited by Clustered Regularly Interspaced Short Palindromic Repeats/associated nuclease Cas9 (CRISPR-Cas9). The effect of the lncRNA silencing will be investigated in the mineralized matrix formation in vitro and on its crosstalk with the Polycomb Repressive Complex 2 (PRC2), with the H3K27me3 epigenetic mark and on osteogenic markers through immunoprecipitation of chromatin and sequencing, and protein levels. In the Part 2, we will make a start in our epigenetic studies on titanium surfaces, treated or not, investigating the pattern of the extracellular mineralized matrix formation, from immortalized and silenced l-PDLCs for the lncRNA MIR31HG, through functional morphologic assays. Since epigenetic mechanisms are plastic and reversible, they can be targeted through individualized drug therapies and functionalization of surfaces to improve regenerative outcomes for patients presenting with bone tissue impairment. (AU)