Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase B-mediated microtubule stabilization.

摘要: We investigated the role of protein kinase B (Akt), a downstream effector phosphatidylinositol 3-kinase, in bone-resorbing activity mature osteoclasts. Treatment with specific Akt inhibitor disrupted sealing zone formation and decreased The normal microtubule structures were lost reduced amount acetylated tubulin, which reflects stabilized microtubules, whereas forced activation by adenovirus vectors resulted opposite effect. Forced increased binding microtubule-associated adenomatous polyposis coli (APC), APC-binding end-binding 1 (EB1) dynactin, dynein activator complex, microtubules. Depletion Akt1 Akt2 disconnection APC/EB1 decrease along formation, both recovered upon addition LiCl, glycogen synthase kinase-3β (GSK-3β) inhibitor. double-knockout mice exhibited osteosclerosis due to bone resorption. These findings indicate that controls osteoclasts stabilizing microtubules via regulation associated proteins.