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HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells
The role of dental pulp cells (DPCs) in hard dental tissue regeneration had received increasing attention because DPCs can differentiate into odontoblasts and other tissue-specific cells. In recent years, epigenetic modifications had been identified to serve an important role in cell differentiation...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780081/ https://www.ncbi.nlm.nih.gov/pubmed/29138868 http://dx.doi.org/10.3892/mmr.2017.8055 |
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author | Liu, Zhao Chen, Ting Han, Qianqian Chen, Ming You, Jie Fang, Fuchun Peng, Ling Wu, Buling |
author_facet | Liu, Zhao Chen, Ting Han, Qianqian Chen, Ming You, Jie Fang, Fuchun Peng, Ling Wu, Buling |
author_sort | Liu, Zhao |
collection | PubMed |
description | The role of dental pulp cells (DPCs) in hard dental tissue regeneration had received increasing attention because DPCs can differentiate into odontoblasts and other tissue-specific cells. In recent years, epigenetic modifications had been identified to serve an important role in cell differentiation, and histone deacetylase (HDAC) inhibitors have been widely studied by many researchers. However, the effects of HDAC4 and HDAC5 on the differentiation of DPCs and the precise molecular mechanisms remain unclear. The present study demonstrated that LMK-235, a specific human HDAC4 and HDAC5 inhibitor, increased the expression of specific odontoblastic gene expression levels detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in dental pulp cells, and did not reduce cell proliferation tested by MTT assay after 3 days in culture at a low concentration. In addition, the mRNA and protein expression levels of dentin sialophosphoprotein, runt-related transcription factor 2, alkaline phosphatase (ALP) and osteocalcin were evaluated by RT-qPCR and western blotting, respectively. The increased gene and protein expression of specific markers demonstrated, indicating that LMK-235 promoted the odontoblast induction of DPCs. ALP activity and mineralised nodule formation were also enhanced due to the effect of LMK-235, detected by an ALP activity test and Alizarin Red S staining, respectively. Additionally, the vascular endothelial growth factor (VEGF)/RAC-gamma serine/threonine-protein kinase (AKT)/mechanistic target of rapamycin (mTOR) signalling pathway was tested to see if it takes part in the differentiation of DPCs treated with LMK-235, and it was demonstrated that the mRNA expression levels of VEGF, AKT and mTOR were upregulated. These findings indicated that LMK-235 may serve a key role in the proliferation and odontoblast differentiation of DPCs, and could be used to accelerate dental tissue regeneration. |
format | Online Article Text |
id | pubmed-5780081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-57800812018-02-12 HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells Liu, Zhao Chen, Ting Han, Qianqian Chen, Ming You, Jie Fang, Fuchun Peng, Ling Wu, Buling Mol Med Rep Articles The role of dental pulp cells (DPCs) in hard dental tissue regeneration had received increasing attention because DPCs can differentiate into odontoblasts and other tissue-specific cells. In recent years, epigenetic modifications had been identified to serve an important role in cell differentiation, and histone deacetylase (HDAC) inhibitors have been widely studied by many researchers. However, the effects of HDAC4 and HDAC5 on the differentiation of DPCs and the precise molecular mechanisms remain unclear. The present study demonstrated that LMK-235, a specific human HDAC4 and HDAC5 inhibitor, increased the expression of specific odontoblastic gene expression levels detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in dental pulp cells, and did not reduce cell proliferation tested by MTT assay after 3 days in culture at a low concentration. In addition, the mRNA and protein expression levels of dentin sialophosphoprotein, runt-related transcription factor 2, alkaline phosphatase (ALP) and osteocalcin were evaluated by RT-qPCR and western blotting, respectively. The increased gene and protein expression of specific markers demonstrated, indicating that LMK-235 promoted the odontoblast induction of DPCs. ALP activity and mineralised nodule formation were also enhanced due to the effect of LMK-235, detected by an ALP activity test and Alizarin Red S staining, respectively. Additionally, the vascular endothelial growth factor (VEGF)/RAC-gamma serine/threonine-protein kinase (AKT)/mechanistic target of rapamycin (mTOR) signalling pathway was tested to see if it takes part in the differentiation of DPCs treated with LMK-235, and it was demonstrated that the mRNA expression levels of VEGF, AKT and mTOR were upregulated. These findings indicated that LMK-235 may serve a key role in the proliferation and odontoblast differentiation of DPCs, and could be used to accelerate dental tissue regeneration. D.A. Spandidos 2018-01 2017-11-14 /pmc/articles/PMC5780081/ /pubmed/29138868 http://dx.doi.org/10.3892/mmr.2017.8055 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Liu, Zhao Chen, Ting Han, Qianqian Chen, Ming You, Jie Fang, Fuchun Peng, Ling Wu, Buling HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title | HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title_full | HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title_fullStr | HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title_full_unstemmed | HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title_short | HDAC inhibitor LMK-235 promotes the odontoblast differentiation of dental pulp cells |
title_sort | hdac inhibitor lmk-235 promotes the odontoblast differentiation of dental pulp cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780081/ https://www.ncbi.nlm.nih.gov/pubmed/29138868 http://dx.doi.org/10.3892/mmr.2017.8055 |
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