TY - JOUR
T1 - Fluoride exposure alters Ca2+ signaling and mitochondrial function in enamel cells
AU - Aulestia, Francisco J.
AU - Groeling, Johnny
AU - Bomfim, Guilherme H.S.
AU - Costiniti, Veronica
AU - Manikandan, Vinu
AU - Chaloemtoem, Ariya
AU - Concepcion, Axel R.
AU - Li, Yi
AU - Wagner, Larry E.
AU - Idaghdour, Youssef
AU - Yule, David I.
AU - Lacruz, Rodrigo S.
N1 - Funding Information:
This work was funded by the National Institute of Dental and Craniofacial Research (NIH/NIDCR) (R01DE025639 and R01DE027679 to R.S.L. and R01DE014756 to D.I.Y.). Y.I. was supported by New York University Abu Dhabi research grant AD105. The NYU Genome Technology Center is partially supported by Cancer Center Support grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
PY - 2020/2/18
Y1 - 2020/2/18
N2 - Fluoride ions are highly reactive, and their incorporation in forming dental enamel at low concentrations promotes mineralization. In contrast, excessive fluoride intake causes dental fluorosis, visually recognizable enamel defects that can increase the risk of caries. To investigate the molecular bases of dental fluorosis, we analyzed the effects of fluoride exposure in enamel cells to assess its impact on Ca2+ signaling. Primary enamel cells and an enamel cell line (LS8) exposed to fluoride showed decreased internal Ca2+ stores and store-operated Ca2+ entry (SOCE). RNA-sequencing analysis revealed changes in gene expression suggestive of endoplasmic reticulum (ER) stress in fluoride-treated LS8 cells. Fluoride exposure did not alter Ca2+ homeostasis or increase the expression of ER stress–associated genes in HEK-293 cells. In enamel cells, fluoride exposure affected the functioning of the ER-localized Ca2+ channel IP3R and the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump during Ca2+ refilling of the ER. Fluoride negatively affected mitochondrial respiration, elicited mitochondrial membrane depolarization, and disrupted mitochondrial morphology. Together, these data provide a potential mechanism underlying dental fluorosis.
AB - Fluoride ions are highly reactive, and their incorporation in forming dental enamel at low concentrations promotes mineralization. In contrast, excessive fluoride intake causes dental fluorosis, visually recognizable enamel defects that can increase the risk of caries. To investigate the molecular bases of dental fluorosis, we analyzed the effects of fluoride exposure in enamel cells to assess its impact on Ca2+ signaling. Primary enamel cells and an enamel cell line (LS8) exposed to fluoride showed decreased internal Ca2+ stores and store-operated Ca2+ entry (SOCE). RNA-sequencing analysis revealed changes in gene expression suggestive of endoplasmic reticulum (ER) stress in fluoride-treated LS8 cells. Fluoride exposure did not alter Ca2+ homeostasis or increase the expression of ER stress–associated genes in HEK-293 cells. In enamel cells, fluoride exposure affected the functioning of the ER-localized Ca2+ channel IP3R and the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump during Ca2+ refilling of the ER. Fluoride negatively affected mitochondrial respiration, elicited mitochondrial membrane depolarization, and disrupted mitochondrial morphology. Together, these data provide a potential mechanism underlying dental fluorosis.
UR - http://www.scopus.com/inward/record.url?scp=85079677112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079677112&partnerID=8YFLogxK
U2 - 10.1126/scisignal.aay0086
DO - 10.1126/scisignal.aay0086
M3 - Article
C2 - 32071168
AN - SCOPUS:85079677112
VL - 13
JO - Science's STKE : signal transduction knowledge environment
JF - Science's STKE : signal transduction knowledge environment
SN - 1937-9145
IS - 619
M1 - eaay0086
ER -