title: Analysis of the Role of Insulin Signaling in Bone Turnover Induced by Fluoride.
abstract: The role of insulin signaling on the mechanism underlying fluoride induced osteopathology was studied. We analyzed the expression of genes related with bone turnover and insulin signaling in rats treated by varying dose of fluoride with or without streptozotocin (STZ) in vivo. Furthermore, insulin receptor (InR) expression in MC3T3-E1 cells (pre-osteoblast cell line) was interfered with small interfering RNA (siRNA), and genes related with osteoblastic and osteoclastic differentiation were investigated in cells exposed to fluoride in vitro for 2 days. The in vivo study indicated the possible role of insulin in bone lesion induced by excessive amount of fluoride. Fluoride activated the InR and Insulin-like growth factor 1 (IGF1) signaling, which were involved in the mechanism underlying fluoride induced bone turnover. The TGFβ1 and Wnt10/β-catenin pathway took part in the mechanism of bone lesion induced by fluoride, and insulin probably modulated the TGFβ1 and β-catenin to exert action on bone turnover during the development of bone lesion. The in vitro study showed the concomitant decrease of OPG, osterix and OCN with inhibition of InR expression in osteoblast, and three genes still was low in cells co-treated with fluoride and InR siRNA, which suggested that fluoride probably stimulated the expression of OPG, osterix and OCN through InR signaling. In conclusion, insulin played the important role in bone lesion induced by excessive amount of fluoride through mediating InR receptor signaling, and IGF1 signaling probably exerted action on bone turnover caused by overdose of fluoride.
authors.affiliation: Department of Orthopedics, the Second Clinical Hospital, Jilin University, Changchun, 130041, China.
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, The First Clinical Hospital, Jilin University, Changchun, 130021, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China. huixujlu@yahoo.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D005459:Fluorides / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D005459:Fluorides
keywords: Bone turnover; Fluoride; Insulin; Insulin receptor; Insulin-like growth factor 1