Cargando…

GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment

Periodontal ligament stem cells (PDLSCs) from periodontitis patients showed defective osteogenic differentiation. However, the mechanism of impaired osteogenic differentiation of PDLSCs in inflammatory microenvironments is still unclear. In this study, we found that inflammation in the microenvironm...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Bei, Sun, Jin, Dong, Zhiwei, Xue, Peng, He, Xiaoning, Liao, Li, Yuan, Lin, Jin, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877597/
https://www.ncbi.nlm.nih.gov/pubmed/27216891
http://dx.doi.org/10.1038/srep26542
_version_ 1782433409628372992
author Li, Bei
Sun, Jin
Dong, Zhiwei
Xue, Peng
He, Xiaoning
Liao, Li
Yuan, Lin
Jin, Yan
author_facet Li, Bei
Sun, Jin
Dong, Zhiwei
Xue, Peng
He, Xiaoning
Liao, Li
Yuan, Lin
Jin, Yan
author_sort Li, Bei
collection PubMed
description Periodontal ligament stem cells (PDLSCs) from periodontitis patients showed defective osteogenic differentiation. However, the mechanism of impaired osteogenic differentiation of PDLSCs in inflammatory microenvironments is still unclear. In this study, we found that inflammation in the microenvironment resulted in downregulation of histone acetyltransferase GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Previous study showed activated Wnt/β-cateinin pathway of PDLSCs resulted in defective osteogenic differentiation. Here we found knockdown of GCN5 decreased the expression of DKK1, an inhibitor of Wnt/β-cateinin pathway, thus activated Wnt/β-catenin pathway of PDLSCs. Mechanistically, GCN5 regulated DKK1 expression by acetylation of Histone H3 lysine 9 (H3K9) and Histone H3 lysine 14 (H3K14) at its promoter region. Interestingly, we found that in vivo injection of aspirin rescued the periodontitis of rats through inhibiting inflammation and upregulating GCN5 expression. Furthermore, aspirin treatment of PDLSCs upregulated GCN5 expression and increased osteogenic differentiation of PDLSCs. In conclusion, GCN5 plays a protective role in periodontitis through acetylation of DKK1 and applying drugs targeting GCN5, such as aspirin, could be a new approach for periodontitis treatment.
format Online
Article
Text
id pubmed-4877597
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-48775972016-06-08 GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment Li, Bei Sun, Jin Dong, Zhiwei Xue, Peng He, Xiaoning Liao, Li Yuan, Lin Jin, Yan Sci Rep Article Periodontal ligament stem cells (PDLSCs) from periodontitis patients showed defective osteogenic differentiation. However, the mechanism of impaired osteogenic differentiation of PDLSCs in inflammatory microenvironments is still unclear. In this study, we found that inflammation in the microenvironment resulted in downregulation of histone acetyltransferase GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Previous study showed activated Wnt/β-cateinin pathway of PDLSCs resulted in defective osteogenic differentiation. Here we found knockdown of GCN5 decreased the expression of DKK1, an inhibitor of Wnt/β-cateinin pathway, thus activated Wnt/β-catenin pathway of PDLSCs. Mechanistically, GCN5 regulated DKK1 expression by acetylation of Histone H3 lysine 9 (H3K9) and Histone H3 lysine 14 (H3K14) at its promoter region. Interestingly, we found that in vivo injection of aspirin rescued the periodontitis of rats through inhibiting inflammation and upregulating GCN5 expression. Furthermore, aspirin treatment of PDLSCs upregulated GCN5 expression and increased osteogenic differentiation of PDLSCs. In conclusion, GCN5 plays a protective role in periodontitis through acetylation of DKK1 and applying drugs targeting GCN5, such as aspirin, could be a new approach for periodontitis treatment. Nature Publishing Group 2016-05-24 /pmc/articles/PMC4877597/ /pubmed/27216891 http://dx.doi.org/10.1038/srep26542 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Bei
Sun, Jin
Dong, Zhiwei
Xue, Peng
He, Xiaoning
Liao, Li
Yuan, Lin
Jin, Yan
GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title_full GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title_fullStr GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title_full_unstemmed GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title_short GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment
title_sort gcn5 modulates osteogenic differentiation of periodontal ligament stem cells through dkk1 acetylation in inflammatory microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877597/
https://www.ncbi.nlm.nih.gov/pubmed/27216891
http://dx.doi.org/10.1038/srep26542
work_keys_str_mv AT libei gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT sunjin gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT dongzhiwei gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT xuepeng gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT hexiaoning gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT liaoli gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT yuanlin gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment
AT jinyan gcn5modulatesosteogenicdifferentiationofperiodontalligamentstemcellsthroughdkk1acetylationininflammatorymicroenvironment