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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase b-mediated microtubule stabilization
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Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase b-mediated microtubule stabilization

机译：破骨细胞中骨吸收和密封区形成的调节是通过蛋白激酶b介导的微管稳定来实现的

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摘要

We investigated the role of protein kinase B (Akt), a downstream effector of phosphatidylinositol 3-kinase, in bone-resorbing activity of mature osteoclasts. Treatment with a specific Akt inhibitor disrupted sealing zone formation and decreased the bone-resorbing activity of osteoclasts. The normal microtubule structures were lost and the Akt inhibitor reduced the amount of acetylated tubulin, which reflects stabilized microtubules, whereas forced Akt activation by adenovirus vectors resulted in the opposite effect. Forced Akt activation increased the binding of the microtubule-associated protein adenomatous polyposis coli (APC), the APC-binding protein end-binding protein 1 (EB1) and dynactin, a dynein activator complex, with microtubules. Depletion of Akt1 and Akt2 resulted in a disconnection of APC/EB1 and a decrease in bone-resorbing activity along with reduced sealing zone formation, both of which were recovered upon the addition of LiCl, a glycogen synthase kinase-3β (GSK-3β) inhibitor. The Akt1 and Akt2 double-knockout mice exhibited osteosclerosis due to reduced bone resorption. These findings indicate that Akt controls the bone-resorbing activity of osteoclasts by stabilizing microtubules via a regulation of the binding of microtubule associated proteins.
机译：我们调查了蛋白激酶B（Akt），磷脂酰肌醇3-激酶的下游效应子在成熟破骨细胞的骨吸收活性中的作用。用特定的Akt抑制剂治疗会破坏密封区域的形成并降低破骨细胞的骨吸收活性。正常的微管结构丢失，Akt抑制剂减少了乙酰化微管蛋白的量，这反映了稳定的微管，而腺病毒载体的强制性Akt激活则产生相反的作用。强迫性Akt激活增加了微管相关蛋白腺瘤性息肉病（APC），APC结合蛋白末端结合蛋白1（EB1）和dynactin（动力蛋白激活剂复合物）与微管的结合。 Akt1和Akt2的耗尽导致APC / EB1的断开和骨吸收活性的降低以及密封区形成的减少，这两者都在加入LiCl（一种糖原合酶激酶3β（GSK-3β））后得以恢复。抑制剂。 Akt1和Akt2双敲除小鼠由于骨吸收减少而显示出骨硬化。这些发现表明，Akt通过调节微管相关蛋白的结合来稳定微管，从而控制破骨细胞的骨吸收活性。

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