Henan Key Laboratory of Environmental and Animal Product Safety, Henan University of Science and Technology, Luoyang, 471000, Henan, People's Republic of China.
Environ Pollut. 2022 Dec 15;315:120396. doi: 10.1016/j.envpol.2022.120396. Epub 2022 Oct 8.
Fluoride (F) exposure can cause osteosclerosis, which is characterised by a high bone mass, but its mechanism is not fully illustrated. Here, we aimed to evaluate the effects of excessive F exposure on the bone lesion by treating female Sprague-Dawley rats with different concentrations of sodium fluoride (NaF) (0, 55, 110 and 221 mg/L) for 90 days and the corresponding concentrations of fluorine ion (0, 25, 50 and 100 mg/L, respectively). Histopathological results showed that excessive F exposure caused the enlargement of trabeculae and their integration into one large piece, growth plate thickening, articular cartilage impairment and bone collagen abnormality. Meanwhile, F promoted calcium deposition and bone mineralisation, and induced abnormal osteogenesis increased. The results of micro-computed tomography also confirmed that excessive F destroyed the bone microstructure and induced a high-bone-mass phenotype, consistent with the results of pathomorphology. Mechanistically, excessive amounts of F led to angiogenesis inhibition and HIF-1α signalling enhancement. Subsequently, F induced autophagy and canonical Wnt/β-catenin signalling pathway activation. Collectively, these results manifested that F enhanced the hypoxia inducible factor-1α signalling, which in turn triggered autophagy and canonical Wnt/β-catenin signalling activation, ultimately leading to osteosclerosis in the rats.
氟化物（F）暴露可导致骨硬化症，其特征为骨量增加，但具体机制尚未完全阐明。在此，我们旨在通过用不同浓度的氟化钠（NaF）（0、55、110 和 221 mg/L）处理雌性 Sprague-Dawley 大鼠 90 天，并相应处理氟离子浓度（0、25、50 和 100 mg/L）来评估过量 F 暴露对骨损伤的影响。组织病理学结果表明，过量 F 暴露导致骨小梁增大并融合成一大块，生长板增厚，关节软骨受损，骨胶原异常。同时，F 促进钙沉积和骨矿化，并诱导异常成骨增加。微计算机断层扫描的结果也证实，过量 F 破坏了骨的微观结构并导致高骨量表型，与形态病理学结果一致。从机制上讲，过量的 F 导致血管生成抑制和 HIF-1α 信号增强。随后，F 诱导自噬和经典 Wnt/β-连环蛋白信号通路激活。总之，这些结果表明 F 增强了缺氧诱导因子-1α 信号，进而触发自噬和经典 Wnt/β-连环蛋白信号通路激活，最终导致大鼠发生骨硬化症。
