title: Fluorosis induces endoplasmic reticulum stress and apoptosis in osteoblasts in vivo.
abstract: The present study investigated the effects of fluoride on endoplasmic reticulum (ER) stress (ERS) and osteoblast apoptosis in vivo. Forty-eight Wistar rats were randomly divided into four groups (12/group) and exposed to 0, 50, 100, and 150 mg/L of fluoride in drinking water for 8 weeks, respectively. Peripheral blood samples and bilateral femurs were used to monitor the progression of fluorosis in the animals. Hematoxylin and eosin (H&E) staining of the bone tissues was used to determine the severity of osteofluorosis. The expression of ERS chaperones (glucose-regulated protein 78 (GRP78), X-box binding protein l (XBP1), cysteine aspartate specific protease-12 (caspase-12), and growth arrest and DNA damage-inducible gene 153 (Gadd153/CHOP) was analyzed by immunohistochemistry staining, and osteoblast apoptosis was determined by TUNEL staining and flow cytometry. Accumulation of fluoride in bone was associated with the severity of osteofluorosis. The expression of GRP78, XBP1, caspase-12, and CHOP was increased in a dose-dependent manner. Fluoride-induced apoptosis in osteoblasts was also dose-dependent. High concentrations of fluoride induced ERS and osteoblast apoptosis in vivo. The increased expression of GRP78 and XBP1 increased the adaptation of osteoblasts to ERS to a certain extent. Caspase-12 and CHOP activation was associated with ERS and osteoblast apoptosis.
authors.affiliation: Department of Preventive Dentistry, School of Stomatology, China Medical University, ShenYang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hefeng
authors.initials: H
authors.lastname: Gu
authors.forename: Kaiqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D005459:Fluorides / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects; D000071717:X-Box Binding Protein 1; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D004268:DNA-Binding Proteins; D005459:Fluorides; D006360:Heat-Shock Proteins; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C000605545:Xbp1 protein, rat