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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis
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Effects of Inositol 1,4,5-triphosphate on Osteoclast Differentiation in RANKL-induced Osteoclastogenesis

机译：肌醇1,4,5-三磷酸对RANKL诱导的破骨细胞生成中破骨细胞分化的影响

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The receptor activator of NF-κB ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-κB and other signal transduction pathways essential for osteoclastogenesis, such as Ca2+ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate (IP3) and IP3-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of IP3 and evaluated IP3-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of Ca2+ signaling proteins such as IP3 receptors (IP3Rs), plasma membrane Ca2+ ATPase, and sarco/endoplasmic reticulum Ca2+ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of IP3 was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) δ, a probe specifically detecting intracellular IP3 levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)] and of IP3Rs with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of IP3Rs) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular IP3 levels and the IP3-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.
机译：NF-κB配体的受体激活剂（RANKL）是肿瘤坏死因子受体相关因子6（TRAF6）的激活剂，可导致NF-κB和其他破骨细胞形成必不可少的信号转导途径的激活，例如Ca sup> 2 + 信令。然而，尚不知道破骨细胞形成过程中肌醇1,4,5-三磷酸（IP 3 ）和IP 3 介导的RANKL的细胞功能水平。在本研究中，我们确定了IP 3 的水平，并通过RANKL处理小鼠白血病巨噬细胞（RAW 264.7）和IP 3 介导的破骨细胞分化和破骨细胞活性进行了评估。小鼠骨髓来源的单核细胞/巨噬细胞前体细胞（BMM）。在破骨细胞形成过程中，Ca 2 + 信号蛋白，如IP 3 受体（IP 3 Rs），质膜Ca 的表达水平两种细胞类型中最多2天，RANKL处理后2 + ATPase和肌浆网/内质网Ca 2 + ATPase type2都没有改变。 RANKL处理后24小时，在转染了磷脂酶C的绿色荧光蛋白（GFP）标记的pleckstrin同源性（PH）域的RAW264.7细胞中，观察到更高的IP 3 稳态水平（ PLC）δ，一种专门检测细胞内IP 3 水平的探针。在BMM中，用U73122 [磷脂酶C（PLC）的特异性抑制剂]抑制PLC，用2-氨基乙氧基二苯基硼酸酯（2APB; IP 的非特异性抑制剂）抑制IP 3 Rs 3 Rs）分别抑制RANKL诱导的多核细胞生成并降低牙本质切片中的骨吸收率。这些结果表明细胞内IP 3 的水平和IP 3 介导的信号通路在RANKL诱导的破骨细胞形成中起重要作用。

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