Abstract：
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.
摘要：
氟化物（F）暴露会导致骨硬化，其特点是骨量大，但其机制尚未完全阐明。这里,我们旨在通过用不同浓度的氟化钠（NaF）（0、55、110和221mg/L）治疗雌性Sprague-Dawley大鼠90天以及相应浓度的氟离子（0、25、50和100mg/L，分别)。组织病理学结果表明，过度的F暴露导致小梁增大并整合成一大块，生长板增厚，关节软骨损伤和骨胶原异常。同时,F促进钙沉积和骨矿化，诱导异常成骨增加。显微计算机断层扫描的结果还证实，过度的F破坏了骨骼的微观结构，并导致了高骨量表型，与病理形态学结果一致。机械上,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-catenin信号通路激活。总的来说，这些结果表明F增强了缺氧诱导因子-1α信号，进而触发自噬和典型的Wnt/β-catenin信号激活，最终导致大鼠骨硬化。
