Epigenetic machinery enzymes expression in osteogenic differentiation initial phase in human mesenchymal cells of the periodontal ligament

• Grant number: 16/03910-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2016
• Effective date (End): May 31, 2017
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Denise Carleto Andia
• Grantee: Francesca Racca
• Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Associated research grant: 13/09650-8 - Epigenetic regulation in human mesenchymal stem cells, AP.JP

Abstract

The scientific community has been focused on the research of human mesenchymal stem cells from periodontal ligament (PDLMSCs) because of its good accessibility, compared to other kinds of stem cells. Studies regarding its isolation and characterization have been growing in the last few years, although its basic biology is not completely understood, mainly regarding epigenetic regulation. The basic mechanism involved in its multipotentiality and indifferentiation is DNA methylation, an epigenetic regulation mechanism. Catalyzed by DNA methyltrasnferases (Dnmts) enzymes, the DNA methylation is a common epigenetic mark and frequently found in CpG sequences. When localized in a gene promoter region it migh be considered as a repressive mark; in addition, a demethylated DNA might be frequently associated to a chromatin active conformation.RG108 is a Dnmt inhibitor that is capable of occupy the active site of Dnmts, blocking the DNA methylation. The Long Interspersed Nuclear Element (LINE) -1 is one of several repetitive sequences from genome. The majority of methylated cytosines is located in repetitive sequences, which is about 40% of human genome, representing a potential threat to the function and genomic stability; in addition, the chromossomal instability might be induced by drugs, leading to the DNA demethylation. The main goal of this research is the PDLMSCs characterization as indifferentiated and multipotent cells and the monitoring of LINE-1 methylation status during the experiment, after changes in the methylation pattern induced by a demethylation agent. (AU)