Kwon Jun-Oh, Lee Yong Deok, Kim Haemin, Kim Min Kyung, Song Min-Kyoung, Lee Zang Hee, Kim Hong-Hee
Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
Biochem Biophys Res Commun. 2016 Sep 2;477(4):1078-1084. doi: 10.1016/j.bbrc.2016.07.046. Epub 2016 Jul 11.
Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules.
四跨膜蛋白家族蛋白在多种细胞类型中调节形态、运动、融合和信号传导。我们研究了四跨膜蛋白7（Tspan7）异构体在破骨细胞分化和功能中的作用。Tspan7在破骨细胞生成过程中上调。当通过siRNA介导的基因敲低使原代前体细胞中的Tspan7表达降低时，多核破骨细胞的生成不受影响。然而，观察到明显的细胞骨架异常：Tspan7敲低抑制了足体带结构的形成，并破坏了微管网络。Tspan7敲低细胞中乙酰化微管的减少以及磷酸化Src和Pyk2水平的降低支持了Tspan7参与破骨细胞的细胞骨架重排信号传导。这种细胞骨架缺陷干扰了封闭区的形成，并随后干扰了成熟破骨细胞在牙本质表面的骨吸收活性。我们的结果表明，Tspan7通过调节向Src、Pyk2和微管的信号传导，在破骨细胞骨吸收功能所需的细胞骨架组织中发挥重要作用。
