Fluoride regulates the expression of extracellular matrix HSPG and related signaling pathways FGFR3 and Ihh/PTHrP feedback loop during endochondral ossification

Publication date: Available online 17 October 2019Source: Environmental Toxicology and PharmacologyAuthor(s): Ying Gao, Fangzhong Gui, Demin Li, Ruixue Zhang, Qinyuan Sun, Xiaoying GuoAbstractSkeletal fluorosis causes growth plate impairment and growth retardation during bone development. Longitudinal bone development is accomplished by endochondral ossification in growth plate. However, the mechanism of fluoride impairs growth plate is unclear. To explore the effect of fluoride on various glycosaminoglycans (GAGs) and related signaling pathways in growth plate during endochondral ossification, SD rats and ATDC5 cells were treated with fluoride and carried out subsequent experiments. We found that the expression of heparan sulfate (HS), a kind of GAGs in extracellular matrix, was significantly increased in the growth plate of fluoride-treated rats compared with control rats. Furthermore, the expression of HS synthetic enzyme exostosin 1 (EXT1) and glypican 6 (GPC6), a core protein of HS proteoglycan (HSPG), were significantly increased in fluoride-treated ATDC5 cells compared with control cells (P < 0.05). The expression of related molecules including fibroblast growth factor receptor-3 (FGFR3), signal transducer and activator of transcription 1 (STAT1) and parathyroid hormone-related protein (PTHrP) were significantly increased in the fluoride-treated groups compared with control groups (P < 0.05), and there was significantly decreased in the expression of In...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research