Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Int J Mol Sci. 2020 Aug 8;21(16):5685. doi: 10.3390/ijms21165685.
Multinucleation is a hallmark of osteoclast maturation. The unique and dynamic multinucleation process not only increases cell size but causes functional alterations through reconstruction of the cytoskeleton, creating the actin ring and ruffled border that enable bone resorption. Our understanding of the molecular mechanisms underlying osteoclast multinucleation has advanced considerably in this century, especially since the identification of DC-STAMP and OC-STAMP as "master fusogens". Regarding the molecules and pathways surrounding these STAMPs, however, only limited progress has been made due to the absence of their ligands. Various molecules and mechanisms other than the STAMPs are involved in osteoclast multinucleation. In addition, several preclinical studies have explored chemicals that may be able to target osteoclast multinucleation, which could enable us to control pathogenic bone metabolism more precisely. In this review, we will focus on recent discoveries regarding the STAMPs and other molecules involved in osteoclast multinucleation.
多核化是破骨细胞成熟的标志。独特而动态的多核化过程不仅增加了细胞大小,还通过细胞骨架的重建引起功能改变,形成肌动蛋白环和皱褶缘,从而实现骨吸收。本世纪以来,我们对破骨细胞多核化的分子机制的理解有了很大进展,特别是自发现 DC-STAMP 和 OC-STAMP 作为“主要融合蛋白”以来。然而,由于缺乏它们的配体,关于这些 STAMPs 周围的分子和途径,仅取得了有限的进展。除了 STAMPs 之外,还有许多其他分子和机制参与了破骨细胞多核化。此外,几项临床前研究已经探索了可能能够针对破骨细胞多核化的化学物质,这可以使我们更精确地控制病理性骨代谢。在这篇综述中,我们将重点介绍有关 STAMPs 和参与破骨细胞多核化的其他分子的最新发现。