title: Role of endoplasmic reticulum stress in aberrant activation of fluoride-treated osteoblasts.
abstract: The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis. The endoplasmic reticulum (ER) stresses and unfolded protein response (UPR) are initiated to alleviate the accumulation of unfolded proteins against cell injury. The previous researches had demonstrated that fluoride induced ER stress in other cells or tissues. In this study, we determined the ER stress and UPR to investigate their roles in aberrant activation of fluoride-treated osteoblasts. The gene expression of bone markers and UPR factors in MC3T3-E1 cells treated with varying doses of fluoride administration was analyzed. Meantime, levels of glutathione and glutathione disulfide were tested by the ultraperformance liquid chromatography-tandem mass spectrometry applications. Our results indicated that a certain dose and period of fluoride administration induced cell proliferation and differentiation, and Runx2 was involved in the regulation of osteoblastic differentiation of MC3T3-E1 cells. Increase trend of Runx2 expression was consistent with change of marker of ER stress. Fluoride caused ER stress and stimulated UPR during the process of osteoblast maturation, while oxidative stress was also active in the occurrence of ER stress. These data indicated that ER stress and UPR were possibly involved in the action of fluoride on osteoblasts.
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yu-lai
authors.initials: YL
authors.lastname: Zhou
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Shi
authors.forename: Xi-ning
authors.initials: XN
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Lv
authors.forename: Guang-sheng
authors.initials: GS
authors.lastname: Li
authors.forename: Qin-yi
authors.initials: QY
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D005459:Fluorides / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D056811:Unfolded Protein Response / Q000187:drug effects* / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D005978:Glutathione; D005459:Fluorides; D019803:Glutathione Disulfide