Aberrant DNA methylation of Cyclind-CDK4-p21 is associated with chronic fluoride poisoning
| Autor: | Bing Qiu, Shouli Wu, Aihua Zhang, Yongfang Liao, Xueli Pan, Yudan Liao, Juan Ming, Weimin Yan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Cyclin-Dependent Kinase Inhibitor p21 Male Population Toxicology 03 medical and health sciences Skeletal fluorosis Fluorides Young Adult 0302 clinical medicine Cyclin D1 Cyclin-dependent kinase medicine Humans education Cyclin Cell Proliferation education.field_of_study Osteoblasts biology Cell Cycle Cyclin-Dependent Kinase 4 General Medicine Methylation Cell cycle DNA Methylation medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Child Preschool DNA methylation Cancer research biology.protein Female Fluoride Poisoning |
| Zdroj: | Chemico-biological interactions. 315 |
| ISSN: | 1872-7786 |
| Popis: | Endemic fluorosis is a serious problem in public health, affecting thousands of people. Abnormal proliferation and activation of osteoblasts in skeletal fluorosis lesions play a leading role and osteoblast proliferation is finely regulated by the cell cycle. There are a few reports on fluoride-induced DNA methylation. However, the role of DNA methylation of the cyclin/cyclin-dependent kinase (CDK)/cyclin-dependent kinase inhibitor (CKI) regulatory network in skeletal fluorosis has not been investigated. We used a population study and in vitro experiment to explore the relationship between the pathogenesis of skeletal fluorosis and methylation of Cyclin d1/CDK4/p21. The results showed a positive relationship between fluoride exposure and expression of Cyclin d1/CDK4, and a negative relationship between fluoride exposure and expression of P21. Hypermethylation of p21 was found in the fluoride-exposed population, and low expression of p21 attributed to promoter hypermethylation was confirmed in vitro. However, no changes in methylation levels of Cyclin d1 and CDK4 genes were observed in the population exposed to fluoride and NaF-treated osteoblasts. These results show that methylation of p21 gene has a significant impact on the proliferation of osteoblasts during the development of skeletal fluorosis. The present study was a first attempt to link the methylation of the Cyclin d1/CDK4/p21 regulatory network with osteoblast proliferation in skeletal fluorosis. |
| Databáze: | OpenAIRE |
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