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Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis

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Title Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis
 
Creator Daiwilea, Atul P.
Taralea, Prashant
Sivanesana, Saravanadevi
Naoghareb, Pravin K.
Bafana, Amit
Parmard, Devendra
Kannana, Krishnamurthi
 
Subject Environmental Health
 
Description Fluoride is an essential trace element required for proper bone and tooth development. Systemic high exposure
to fluoride through environmental exposure (drinking water and food) may result in toxicity causing a disorder
called fluorosis. In the present study, we investigated the alteration in DNA methylation profile with chronic
exposure (30 days) to fluoride (8 mg/l) and its relevance in the development of fluorosis. Whole genome bisulfite
sequencing (WGBS) was carried out in human osteosarcoma cells (HOS) exposed to fluoride. Whole genome
bisulfite sequencing (WGBS) and functional annotation of differentially methylated genes indicate alterations in
methylation status of genes involved in biological processes associated with bone development pathways.
Combined analysis of promoter DNA hyper methylation, STRING: functional protein association networks and
gene expression analysis revealed epigenetic alterations in BMP1, METAP2, MMP11 and BACH1 genes, which
plays a role in the extracellular matrix disassembly, collagen catabolic/organization process, skeletal morphogenesis/
development, ossification and osteoblast development. The present study shows that fluoride causes
promoter DNA hypermethylation in BMP1, METAP2, MMP11 and BACH1 genes with subsequent down-regulation
in their expression level (RNA level). The results implies that fluoride induced DNA hypermethylation of
these genes may hamper extracellular matrix deposition, cartilage formation, angiogenesis, vascular system
development and porosity of bone, thus promote skeletal fluorosis.
 
Publisher Elsevier
 
Date 2019
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://neeri.csircentral.net/1148/1/1-s2.0-S0147651318311734-main.pdf
Daiwilea, Atul P. and Taralea, Prashant and Sivanesana, Saravanadevi and Naoghareb, Pravin K. and Bafana, Amit and Parmard, Devendra and Kannana, Krishnamurthi (2019) Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis. Ecotoxicology and Environmental Safety, 169. pp. 410-417. ISSN 0147-6513
 
Relation http://www.elsevier.com/locate/ecoenv
http://neeri.csircentral.net/1148/