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DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells.
Assis, Rahyza I F; Schmidt, Arthur G; Racca, Francesca; da Silva, Rodrigo A; Zambuzzi, William F; Silvério, Karina G; Nociti, Francisco H; Pecorari, Vanessa G; Wiench, Malgorzata; Andia, Denise C.
Afiliação
  • Assis RIF; Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
  • Schmidt AG; Health Science Institute, School of Dentistry, Paulista University-UNIP, São Paulo, Brazil.
  • Racca F; Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
  • da Silva RA; Program in Environmental and Experimental Pathology, Paulista University-UNIP, São Paulo, Brazil.
  • Zambuzzi WF; Department of Chemistry and Biochemistry, Biosciences Institute, São Paulo State University, Botucatu, Brazil.
  • Silvério KG; Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
  • Nociti FH; Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
  • Pecorari VG; Health Science Institute, School of Dentistry, Paulista University-UNIP, São Paulo, Brazil.
  • Wiench M; Institute of Clinical Sciences, Institute of Cancer and Genomic Sciences, School of Dentistry, University of Birmingham, Birmingham, United Kingdom.
  • Andia DC; Health Science Institute, School of Dentistry, Paulista University-UNIP, São Paulo, Brazil.
DNA Cell Biol ; 40(5): 662-674, 2021 May.
Article em En | MEDLINE | ID: mdl-33751901
Periodontal ligament cells (PDLCs) have well documented osteogenic potential; however, this commitment can be highly heterogenous, limiting their applications in tissue regeneration. In this study, we use PDLC populations characterized by high and low osteogenic potential (h-PDLCs and l-PDLCs, respectively) to identify possible sources of such heterogeneity and to investigate whether the osteogenic differentiation can be enhanced by epigenetic modulation. In h-PDLCs, low basal expression levels of pluripotency markers (NANOG, OCT4), DNA methyltransferases (DNMT1, DNMT3B), and enzymes involved in active DNA demethylation (TET1, TET3) were prerequisite to high osteogenic potential. Furthermore, these genes were downregulated upon early osteogenesis, possibly allowing for the increase in expression of the key osteogenic transcription factors, Runt-related transcription factor 2 (RUNX2) and SP7, and ultimately, mineral nodule formation. l-PDLCs appeared locked in the multipotent state and this was further enhanced upon early osteogenic stimulation, correlating with low RUNX2 expression and impaired mineralization. Further upregulation of DNMTs was also evident, while pretreatment with RG108, the DNMTs' inhibitor, enhanced the osteogenic program in l-PDLCs through downregulation of DNMTs, increased RUNX2 expression and nuclear localization, accelerated expression of osteogenic markers, and increased mineralization. These findings point toward the role of DNMTs and Ten Eleven Translocations (TETs) in osteogenic commitment and support application of epigenetic approaches to modulate biomineralization in PDLCs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ligamento Periodontal / Calcificação Fisiológica / Inibidores Enzimáticos / Subunidade alfa 1 de Fator de Ligação ao Core / DNA (Citosina-5-)-Metiltransferase 1 Tipo de estudo: Prognostic_studies Limite: Adult / Humans Idioma: En Revista: DNA Cell Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ligamento Periodontal / Calcificação Fisiológica / Inibidores Enzimáticos / Subunidade alfa 1 de Fator de Ligação ao Core / DNA (Citosina-5-)-Metiltransferase 1 Tipo de estudo: Prognostic_studies Limite: Adult / Humans Idioma: En Revista: DNA Cell Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos