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Effects of fluoride on expression of bone-specific genes in developing Xenopus laevis larvae.

机译:氟化物对南欧省幼虫发展骨特异性基因表达的影响。

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The effect of fluoride treatment on the expression of a panel of osteogenic and stress markers in Stage 55 premetamorphic Xenopus larvae was examined at the precise onset of replacement of the larval cartilaginous skeleton with bone. A dosing regimen of 10 mmol/L sodium fluoride over 8 days was followed, during which time larvae developed to Stage 58, when the process of progressive ossification takes place in the vertebral column and membranous bones of the skull, pelvic, and pectoral girdles and portions of the appendicular skeleton. Markers of bone formation, including COL1A1, the transcription factors Osterix, RUNX2-II, and matrix metalloproteinases MMP1 and MMP13, decreased relative to age-matched controls, though the osteoblast marker BGLAP was not significantly altered. Expression of the pro-osteoclastogenic factor RANKL decreased, whereas expression of the anti-osteoclastogenic factor osteoprotegerin increased. Altered expression of oxidative stress markers, with the exception of superoxide dismutase, was generally not observed. These data demonstrate the potent effects of fluoride on the expression of factors required for osteoblast and osteoclast differentiation, as well as on the expression of osteoblast products, including MMP1 and collagen. Importantly, these effects were observed in the absence of significant changes in the expression of oxidative stress markers. The results provide the first molecular insights into the mechanisms underlying skeletal fluorosis in a whole organism developmental model.
机译:氟化物处理对55阶段牙尾幼虫在第55阶段骨质骨质和应激标志物的表达的影响是在用骨骼的精确替代幼虫软骨骨架的精确发作。遵循10mmol / L氟化钠超过8天的给药方案,在此期间幼虫发育到第58阶段,当在头骨,盆腔,骨盆和胸颈部的椎体柱和膜骨和膜骨中发生逐步58时阑尾骨骼的部分。骨形成的标记,包括COL1A1,转录因子Osterix,RunX2-II和基质金属蛋白酶MMP1和MMP13,相对于年龄匹配的对照减少,但没有显着改变。促骨溶源性因子RANK1的表达降低,而抗骨酮化因子骨酮素的表达增加。除了超氧化物歧化酶外,通常未观察到改变氧化应激标记物的表达。这些数据表明了氟化物对成骨细胞和破骨细胞分化所需的因子表达的有效效果,以及骨喷制品的表达,包括MMP1和胶原。重要的是,在没有显着变化的氧化应激标记物的表达的情况下观察到这些效果。结果为整个生物发育模型中的骨骼氟中毒的潜在机制提供了第一种分子见解。

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