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首页> 外文期刊>Cell biology international. >Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody
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Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody

机译:阿米洛利和NHE10特异性单克隆抗体对破骨细胞中RANKL依赖性细胞融合的抑制作用

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摘要

The functions of Na+/H+ exchangers (NHEs) during osteoclastic differentiation were investigated using the NHE inhibitor amiloride and a monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells, amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with 10 nuclei and increased the number of small TRAP-positive OCs with 10 nuclei during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10 mRNA expression and OC differentiation markers were increased by sRANKL stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the number of small TRAP-positive OCs. These findings suggested that inhibition of NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion. The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone resorption for targeted bone disease therapy.
机译:使用NHE抑制剂阿米洛利和单克隆抗体(MAb),研究了Na + / H +交换子(NHE)在破骨细胞分化过程中的功能。与sRANKL刺激的对照细胞相比,在RAW264.7细胞的sRANKL依赖性破骨细胞分化过程中,阿米洛利减少了具有10个核的大TRAP阳性破骨细胞(OCs)的数量,并增加了具有10个核的小型TRAP阳性OCs的数量。 sRANKL刺激以剂量和时间依赖性方式增加NHE10 mRNA表达和OC分化标志物。 sRANKL刺激不会增加NHEs 1-9 mRNA的表达。与阿米洛利相似,大鼠抗小鼠NHE10 MAb(克隆6B11)减少了大TRAP阳性OC的数量,但增加了小TRAP阳性OC的数量。这些发现表明,阿米洛利或抗NHE10 MAb对NHE的抑制作用阻止了sRANKL促进的细胞融合。抗NHE10 MAb有潜力用作靶向骨病治疗的有效骨吸收抑制剂。

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