DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorPaulista Univ UNIP-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniv Birmingham-
Autor(es): dc.creatorAssis, Rahyza I. F.-
Autor(es): dc.creatorSchmidt, Arthur G.-
Autor(es): dc.creatorRacca, Francesca-
Autor(es): dc.creatorSilva, Rodrigo A. da-
Autor(es): dc.creatorZambuzzi, William F. [UNESP]-
Autor(es): dc.creatorSilverio, Karina G.-
Autor(es): dc.creatorNociti, Francisco H.-
Autor(es): dc.creatorPecorari, Vanessa G.-
Autor(es): dc.creatorWiench, Malgorzata-
Autor(es): dc.creatorAndia, Denise C.-
Data de aceite: dc.date.accessioned2022-02-22T00:58:41Z-
Data de disponibilização: dc.date.available2022-02-22T00:58:41Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-03-22-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1089/dna.2020.6239-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/210148-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/210148-
Descrição: dc.descriptionPeriodontal 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.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionUniversity of Birmingham, United Kingdom-
Descrição: dc.descriptionUniv Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, Piracicaba, Brazil-
Descrição: dc.descriptionPaulista Univ UNIP, Sch Dent, Hlth Sci Inst, Dr Bacelar St 1212, BR-04026002 Sao Paulo, Brazil-
Descrição: dc.descriptionPaulista Univ UNIP, Program Environm & Expt Pathol, Sao Paulo, Brazil-
Descrição: dc.descriptionSao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil-
Descrição: dc.descriptionUniv Birmingham, Sch Dent, Inst Canc & Genom Sci, Inst Clin Sci, 5 Mill Pool Way, Birmingham B5 7EG, W Midlands, England-
Descrição: dc.descriptionSao Paulo State Univ, Biosci Inst, Dept Chem & Biochem, Botucatu, SP, Brazil-
Descrição: dc.descriptionFAPESP: 2013/09650-8-
Descrição: dc.descriptionFAPESP: 2017/07944-5-
Descrição: dc.descriptionUniversity of Birmingham, United Kingdom: 2017/07944-5-
Descrição: dc.descriptionFAPESP: 2015/02160-0-
Formato: dc.format13-
Idioma: dc.languageen-
Publicador: dc.publisherMary Ann Liebert, Inc-
Relação: dc.relationDna And Cell Biology-
???dc.source???: dc.sourceWeb of Science-
Palavras-chave: dc.subjectperiodontal ligament stem cells-
Palavras-chave: dc.subjectosteogenic potential-
Palavras-chave: dc.subjectRUNX2-
Palavras-chave: dc.subjectDNA methyltransferases-
Palavras-chave: dc.subjectRG108-
Título: dc.titleDNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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