Department of Biochemistry, Matsumoto Dental University, Nagano, 399-0781, Japan.
Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan.
Cell Mol Life Sci. 2018 Oct;75(20):3683-3692. doi: 10.1007/s00018-018-2881-1. Epub 2018 Jul 26.
Osteoclasts are multinucleated cells responsible for bone resorption. Osteoclasts adhere to the bone surface through integrins and polarize to form actin rings, which are formed by the assembly of podosomes. The area contained within actin rings (also called sealing zones) has an acidic pH, which causes dissolution of bone minerals including hydroxyapatite and the degradation of matrix proteins including type I collagen by the protease cathepsin K. Osteoclasts resorb bone matrices while moving on bone surfaces. Osteoclasts change their cell shapes and exhibit three modes for bone resorption: motile resorbing mode for digging trenches, static resorbing mode for digging pits, and motile non-resorbing mode. Therefore, the actin cytoskeleton is actively remodeled in osteoclasts. Recent studies have revealed that many molecules, such as Rac, Cdc42, Rho, and small GTPase regulators and effectors, are involved in actin cytoskeletal remodeling during the formation of actin rings and resorption cavities on bone slices. In this review, we introduce how these molecules and non-canonical Wnt signaling regulate the bone-resorbing activity of osteoclasts.
破骨细胞是负责骨吸收的多核细胞。破骨细胞通过整合素附着在骨表面，并极化形成由 podosomes 组装而成的肌动蛋白环。肌动蛋白环（也称为封闭带）所包含的区域呈酸性 pH 值，导致包括羟基磷灰石在内的骨矿物质溶解，以及包括 I 型胶原在内的基质蛋白降解，由蛋白酶组织蛋白酶 K 引起。破骨细胞在骨表面移动的同时吸收骨基质。破骨细胞改变其细胞形状，并表现出三种骨吸收模式：挖掘沟渠的运动吸收模式、挖掘坑的静态吸收模式和运动非吸收模式。因此，破骨细胞中的肌动蛋白细胞骨架被积极重塑。最近的研究表明，许多分子，如 Rac、CDC42、Rho 和小 GTPase 调节剂和效应物，参与了骨切片上肌动蛋白环和吸收腔形成过程中的肌动蛋白细胞骨架重塑。在这篇综述中，我们介绍了这些分子和非经典 Wnt 信号如何调节破骨细胞的骨吸收活性。
