The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption.
The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption.
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DOI：
10.3389/fcell.2021.644503
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发表时间：
2021
影响因子：
5.5
通讯作者：
Marcussen N
中科院分区：
文献类型：
--
作者：
Delaisse JM;Søe K;Andersen TL;Rojek AM;Marcussen N
目前破骨细胞性骨吸收的模型主要集中在固定的破骨细胞位于骨表面，并在骨基质中钻入一个凹坑。最近的研究表明，许多破骨细胞也通过在吸收时在骨表面移动来扩大它们的凹陷。因此，钻探矿坑只代表着一场幅度大得多的再吸收事件的开始。这种长期的吸收活动显著地促进了病理性的骨破坏，但破骨细胞参与这一过程的机制在标准的骨吸收模型中还没有答案。在这里，我们回顾了导致设想如何通过同时吸收和迁移来延长吸收的观察结果。根据标准凹坑模型，围绕皱纹边缘(即实际的吸收装置)的“密封区”将皱纹边缘“锚定”在待吸收的骨表面上。在这里，我们强调持续的吸收需要密封区在腔内“滑动”。因此，密封区作为负责定向和移位褶皱边缘的结构出现，例如，将吸收引向腔壁。重要的是，封闭区移位严格要求从洞壁彻底去除胶原蛋白，这使得强大的组织蛋白酶K胶原酶溶解对于破骨细胞参与洞扩大是必不可少的。此外，密封区与在前缘产生新的褶边相关联，从而允许褶边向前移动。封闭带和褶皱的边缘位移与细胞体的迁移相协调，显示出在前缘受片状脂膜控制，在后面受吸收产物的释放控制。我们认为，骨吸收需要更多地关注将吸收和迁移活动整合为一种细胞表型的破骨细胞模型。
The current models of osteoclastic bone resorption focus on immobile osteoclasts sitting on the bone surface and drilling a pit into the bone matrix. It recently appeared that many osteoclasts also enlarge their pit by moving across the bone surface while resorbing. Drilling a pit thus represents only the start of a resorption event of much larger amplitude. This prolonged resorption activity significantly contributes to pathological bone destruction, but the mechanism whereby the osteoclast engages in this process does not have an answer within the standard bone resorption models. Herein, we review observations that lead to envision how prolonged resorption is possible through simultaneous resorption and migration. According to the standard pit model, the “sealing zone” which surrounds the ruffled border (i.e., the actual resorption apparatus), “anchors” the ruffled border against the bone surface to be resorbed. Herein, we highlight that continuation of resorption demands that the sealing zone “glides” inside the cavity. Thereby, the sealing zone emerges as the structure responsible for orienting and displacing the ruffled border, e.g., directing resorption against the cavity wall. Importantly, sealing zone displacement stringently requires thorough collagen removal from the cavity wall - which renders strong cathepsin K collagenolysis indispensable for engagement of osteoclasts in cavity-enlargement. Furthermore, the sealing zone is associated with generation of new ruffled border at the leading edge, thereby allowing the ruffled border to move ahead. The sealing zone and ruffled border displacements are coordinated with the migration of the cell body, shown to be under control of lamellipodia at the leading edge and of the release of resorption products at the rear. We propose that bone resorption demands more attention to osteoclastic models integrating resorption and migration activities into just one cell phenotype.
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