Tetraspanin 7 regulates osteoclast function through association with the RANK/αvβ3 integrin complex,Journal of Cellular Physiology

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Tetraspanin 7 regulates osteoclast function through association with the RANK/αvβ3 integrin complex
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-08-18 , DOI: 10.1002/jcp.30559
Minhee Kim _{1,

2} , Jingjing Lin _{1,

2} , Jeong-Eun Huh _{1,

2} , Jin Hee Park _{1,

2} , Miyeon Go _{1,

2} , Hana Lee ₃ , Donghyun Hwang ₃ , Han Sung Kim ₃ , Taesoo Kim _{1,

2} , Daekee Lee ₁ , Soo Young Lee _{1,

2}

Affiliation

Actin rings are unique structures that facilitate the attachment of osteoclasts to the bone matrix during bone resorption. Previous studies have shown that tetraspanin7 (TSPAN7) plays an important role in the reorganization of the cytoskeleton necessary for the bone-resorbing activity of osteoclasts. However, questions remain as to the mechanisms by which TSPAN7 regulates this cytoskeletal rearrangement. In this study, we investigated the roles of TSPAN7 in osteoclasts by deleting the Tm4sf2 gene in mice, which encodes TSPAN7. The Tm4sf2 global knockout model showed protective effects on pathological bone loss, but no discernible changes in bone phenotypes under physiological conditions. In vitro study revealed that ablation of Tm4sf2 caused significant defects in integrin-mediated actin ring formation, thereby leading to significantly decreased bone resorption. Additionally, we demonstrated an association between TSPAN7 and the receptor activator of nuclear factor-кB/αvβ3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.

中文翻译：

Tetraspanin 7 通过与 RANK/αvβ3 整合素复合物结合来调节破骨细胞功能

肌动蛋白环是一种独特的结构，可在骨吸收过程中促进破骨细胞与骨基质的附着。先前的研究表明，四跨膜蛋白7 (TSPAN7) 在破骨细胞的骨吸收活性所必需的细胞骨架重组中起重要作用。然而，关于 TSPAN7 调节这种细胞骨架重排的机制仍然存在疑问。在这项研究中，我们通过删除小鼠中编码 TSPAN7的Tm4sf2基因来研究 TSPAN7 在破骨细胞中的作用。Tm4sf2全局敲除模型显示出对病理性骨丢失的保护作用，但在生理条件下骨表型没有明显变化。体外研究表明，消融Tm4sf2导致整合素介导的肌动蛋白环形成的显着缺陷，从而导致骨吸收显着降低。此外，我们证明了 TSPAN7 与核因子-кB/αvβ3 整合素受体激活剂之间的关联。总体而言，我们的研究结果表明，TSPAN7 是一种调节破骨细胞骨吸收功能的新型调节剂。

更新日期：2021-08-18

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