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Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1
INTRODUCTION: Fluoride can induce the proliferation and activation of osteoblasts, resulting in skeletal fluorosis progression; however, the specific mechanism is unclear. METHODS: Cell proliferation was examined using the MTT assay. Flow cytometry was performed to detect the cell cycle distribution...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japanese Society for Regenerative Medicine
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814769/ https://www.ncbi.nlm.nih.gov/pubmed/35155723 http://dx.doi.org/10.1016/j.reth.2022.01.004 |
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author | Chen, Long Yin, Na Ding, Yi Zhang, Mei-Lin Li, Min Zhong, Jin-Jie Feng, Shu-Mei |
author_facet | Chen, Long Yin, Na Ding, Yi Zhang, Mei-Lin Li, Min Zhong, Jin-Jie Feng, Shu-Mei |
author_sort | Chen, Long |
collection | PubMed |
description | INTRODUCTION: Fluoride can induce the proliferation and activation of osteoblasts, resulting in skeletal fluorosis progression; however, the specific mechanism is unclear. METHODS: Cell proliferation was examined using the MTT assay. Flow cytometry was performed to detect the cell cycle distribution. Alkaline phosphatase (ALP) was calculated to evaluate bone formation and turnover. Gene methylation was examined using the MSP assay. mRNA and protein expression levels were assessed using qRT-PCR and Western blot assays. RESULTS: Low-concentration NaF treatment promoted the cell cycle progression of osteoblasts to S-phase, thus accelerating cell proliferation and activation in a concentration-dependent manner. In addition, the methylation of the MGMT and MLH1 genes was increased, and their mRNA expression was reduced. Furthermore, the DNA methyltransferase inhibitor 5-AZA-dC suppressed cell viability, cell number in S-phase, ALP activity and osteogenesis-related protein levels in osteoblasts treated with low doses of NaF. Meanwhile, 5-AZA-dC suppressed the increase in MGMT and MLH1 gene methylation in osteoblasts treated with low doses of NaF, leading to enhanced expression of MGMT and MLH1 mRNA. CONCLUSION: NaF treatment led to methylation of the DNA repair genes MGMT and MLH1 in osteoblasts, resulting in cell proliferation and activation and causing the development of skeletal fluorosis. |
format | Online Article Text |
id | pubmed-8814769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Japanese Society for Regenerative Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-88147692022-02-11 Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 Chen, Long Yin, Na Ding, Yi Zhang, Mei-Lin Li, Min Zhong, Jin-Jie Feng, Shu-Mei Regen Ther Original Article INTRODUCTION: Fluoride can induce the proliferation and activation of osteoblasts, resulting in skeletal fluorosis progression; however, the specific mechanism is unclear. METHODS: Cell proliferation was examined using the MTT assay. Flow cytometry was performed to detect the cell cycle distribution. Alkaline phosphatase (ALP) was calculated to evaluate bone formation and turnover. Gene methylation was examined using the MSP assay. mRNA and protein expression levels were assessed using qRT-PCR and Western blot assays. RESULTS: Low-concentration NaF treatment promoted the cell cycle progression of osteoblasts to S-phase, thus accelerating cell proliferation and activation in a concentration-dependent manner. In addition, the methylation of the MGMT and MLH1 genes was increased, and their mRNA expression was reduced. Furthermore, the DNA methyltransferase inhibitor 5-AZA-dC suppressed cell viability, cell number in S-phase, ALP activity and osteogenesis-related protein levels in osteoblasts treated with low doses of NaF. Meanwhile, 5-AZA-dC suppressed the increase in MGMT and MLH1 gene methylation in osteoblasts treated with low doses of NaF, leading to enhanced expression of MGMT and MLH1 mRNA. CONCLUSION: NaF treatment led to methylation of the DNA repair genes MGMT and MLH1 in osteoblasts, resulting in cell proliferation and activation and causing the development of skeletal fluorosis. Japanese Society for Regenerative Medicine 2022-01-30 /pmc/articles/PMC8814769/ /pubmed/35155723 http://dx.doi.org/10.1016/j.reth.2022.01.004 Text en © 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Chen, Long Yin, Na Ding, Yi Zhang, Mei-Lin Li, Min Zhong, Jin-Jie Feng, Shu-Mei Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title | Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title_full | Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title_fullStr | Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title_full_unstemmed | Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title_short | Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1 |
title_sort | effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the dna repair genes mgmt and mlh1 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814769/ https://www.ncbi.nlm.nih.gov/pubmed/35155723 http://dx.doi.org/10.1016/j.reth.2022.01.004 |
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