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首页> 外文期刊>Journal of Cellular Physiology >Effect of l l ‐caldesmon on osteoclastogenesis in RANKL–induced RAW264.7 cells
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Effect of l l ‐caldesmon on osteoclastogenesis in RANKL–induced RAW264.7 cells

机译：l l在osteoclastogenesis caldesmon应承担的效果RANKL-induced RAW264.7细胞

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摘要

Non‐muscle caldesmon (l‐CaD) is involved in the regulation of actin cytoskeletal remodeling in the podosome formation, but its function in osteoclastogenesis remains to be determined. In this study, RANKL‐induced differentiation of RAW264.7 murine macrophages to osteoclast‐like cells (OCs) was used as a model to determine the physiological role of l‐CaD and its phosphorylation in osteoclastogenesis. Upon RANKL treatment, RAW264.7 cells undergo cell‐cell fusion into multinucleate, and TRAP‐positive large OCs with a concomitant increase of l‐CaD expression. Using gain‐ and loss‐of‐function in OC precursor cells followed by RANKL induction, we showed that the expression of l‐CaD in response to RANKL activation is an important event for osteoclastogenesis, and bone resorption. To determine the effect of l‐CaD phosphorylation in osteoclastogenesis, three decoy peptides of l‐CaD were used with, respectively, Ser‐to‐Ala mutations at the Erk‐ and Pak1‐mediated phosphorylation sites, and Ser‐to‐Asp mutation at the Erk‐mediated phosphorylation sites. Both the former two peptides competed with the C‐terminal segment of l‐CaD for F‐actin binding and accelerated formation of podosome‐like structures in RANKL‐induced OCs, while the third peptide did not significantly affect the F‐actin binding of l‐CaD, and decreased the formation of podosome‐like structures in OCs. With the experiments using dephosphorylated and phosphorylated l‐CaD mutants, we further showed that dephosphorylated l‐CaD mutant facilitated RANKL‐induced TRAP activity with an increased cell fusion index, whereas phosphorylated l‐CaD decreased the TRAP activity and cell fusion. Our findings suggested that both the level of l‐CaD expression and the extent of l‐CaD phosphorylation play a role in RANKL‐induced osteoclast differentiation.
机译：非肌肉caldesmon应承担(l必经CaD)是参与调节肌动蛋白细胞骨架重塑podosome形成,但它的功能osteoclastogenesis仍有待确定。这项研究中,RANKL的诱导分化RAW264.7小鼠巨噬细胞,破骨细胞的类细胞(OCs)被用作模型来确定l CaD及其应承担的生理作用在osteoclastogenesis磷酸化。治疗,RAW264.7细胞进行细胞的细胞融合到多核的,陷阱还是积极的大陆棚的同时增加l CaD表达式。OC前驱细胞RANKL感应紧随其后,我们表明,l的表达CaD应对RANKL激活是一个重要的事件为osteoclastogenesis和骨头吸收。在osteoclastogenesis磷酸化,三人l使用CaD与假肽,分别Ser ~ Ala突变量Erk所致然后Pak1介导的磷酸化网站,Ser ~公/ Asp Erk必经介导突变磷酸化的网站。肽与C的终端部分l CaD F肌动蛋白绑定和加速podosome的类结构的形成RANKL应承担的诱导,而第三肽F肌动蛋白绑定等无明显影响l高CaD和减少的形成在大一podosome类结构。实验使用脱去磷酸和磷酸化l高CaD突变体在我们进一步显示脱去磷酸l CaD变异了RANKL诱导陷阱活动增加细胞融合指数,而磷酸化l CaD降低了陷阱活动和细胞融合。研究结果表明,l CaD应承担的水平表达和l CaD应承担的程度磷酸化在RANKL中发挥作用的诱导破骨细胞分化。

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