Osteoclasts are responsible for bone resorption and play an important role in physiological and pathological bone metabolism. Osteoclast migration across bone surfaces is essential for bone resorption, and a previous study demonstrated the role of autophagy in osteoclastogenesis and acid secretion. However, the role of autophagy in osteoclast migration remains unclear. Osteoclast migration requires the successive and rapid assembly and disassembly of podosome rings. In this study, we show that kindlin3, an important adaptor protein in the podosome, can interact with LC3B and undergo autophagy-mediated protein degradation to promote the disassembly of the podosome. Moreover, further analyses showed that the inhibition of autophagy increased kindlin3 levels and enhanced the interaction between kindlin3 and integrin β3. The over activation of integrins inhibits the disassembly of obsolete podosome rings, resulting in disorganization of the actin cytoskeleton and impaired migration in osteoclasts. Our results show that LC3B affects osteoclast migration and FAK/AKT activation by modulating integrin activation via a kindlin3-mediated inside-out signal from the extracellular matrix. Based on these results, we propose that LC3 is an important target for regulating osteoclast migration.

中文翻译：

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自噬通过kindlin3与LC3的相互作用促进破骨细胞足体的分解和细胞运动。

破骨细胞负责骨吸收，并在生理和病理性骨代谢中起重要作用。破骨细胞跨骨表面迁移对于骨吸收至关重要，先前的研究表明自噬在破骨细胞生成和酸分泌中的作用。然而，自噬在破骨细胞迁移中的作用仍不清楚。破骨细胞的迁移需要足小体环的连续快速组装和拆卸。在这项研究中，我们表明，kinodlin3是足小体中的重要衔接蛋白，可以与LC3B相互作用并经历自噬介导的蛋白质降解，从而促进足小体的拆卸。此外，进一步的分析表明自噬的抑制增加了kindlin3水平并增强了kindlin3与整联蛋白β3之间的相互作用。整联蛋白的过度激活抑制了过时的足小体环的分解，从而导致肌动蛋白细胞骨架的紊乱和破骨细胞的迁移受损。我们的研究结果表明，LC3B通过调节来自细胞外基质的kindlin3介导的由内而外的信号来调节整联蛋白的激活，从而影响破骨细胞的迁移和FAK / AKT的激活。基于这些结果，我们认为LC3是调节破骨细胞迁移的重要靶标。