Jurdic Pierre, Saltel Frédéric, Chabadel Anne, Destaing Olivier
Laboratoire de Biologie Moléculaire et Cellulaire UMR 5161 CNRS/ENS, IFR 128 Biosciences, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, F-69007 Lyon, France.
Eur J Cell Biol. 2006 Apr;85(3-4):195-202. doi: 10.1016/j.ejcb.2005.09.008. Epub 2005 Oct 24.
The bone resorption function of osteoclasts is dependent on the integrity of the actin cytoskeleton. Depending on the substratum upon which the osteoclasts are spread, there are two different structures of actin known as podosomes and the sealing zone. To understand the specific properties and relationship of podosomes and the sealing zone, we used live-cell imaging of cultured osteoclasts. When cultured on extracellular matrix components, podosomes in these cells are organized in higher-ordered structures. These are clustered podosomes that will arrange later into dynamic short-lived rings which finally expand to the cell periphery to form a stable long-lived podosome belt in fully differentiated cells. In osteoclasts, this specific podosome patterning is under the control of microtubules (MTs). Indeed, nocodazole treatment does not affect podosome formation but only the transition between clusters/rings and belts. During this transition, MTs accumulate a specific post-translational modification of tubulin by acetylation. This process is repressed by an inhibitory pathway involving the GTPase Rho, its effector mDIA2 and the recently discovered tubulin deacetylase HDAC6. The specific function of this acetylation is still unknown but is also observed in active osteoclasts forming a sealing zone which is also MT dependent. Thus, it appears that the podosome belt is reminiscent of the sealing zone. Indeed, podosome belts and sealing zones are characterized by their overall stability. Despite their similar behavior, a sealing zone is not formed by fusion of podosomes. The formation of a podosome belt or a sealing zone is controlled by the external environment. Indeed, only the bone mineral fraction, known as apatite crystal, is able to induce sealing zone formation in mature osteoclasts. Contact of osteoclasts with apatite stimulates the non-receptor tyrosine kinase c-Src and the GTPase Rho in order to form the sealing zone. As we will discuss in this review, it appears that podosomes and the sealing zone are strikingly linked.
破骨细胞的骨吸收功能依赖于肌动蛋白细胞骨架的完整性。根据破骨细胞铺展的基质不同，存在两种不同的肌动蛋白结构，即足体和封闭带。为了解足体和封闭带的具体特性及关系，我们对培养的破骨细胞进行了活细胞成像。当在细胞外基质成分上培养时，这些细胞中的足体会形成更高层次的结构。这些是聚集的足体，随后会排列成动态的短命环，最终扩展到细胞周边，在完全分化的细胞中形成稳定的长寿足体带。在破骨细胞中，这种特定的足体模式受微管（MTs）控制。事实上，诺考达唑处理并不影响足体的形成，而只影响簇/环与带之间的转变。在这个转变过程中，微管会积累微管蛋白通过乙酰化的特定翻译后修饰。这个过程受到一条抑制途径的抑制，该途径涉及GTP酶Rho、其效应器mDIA2和最近发现的微管蛋白去乙酰化酶HDAC6。这种乙酰化的具体功能仍然未知，但在形成同样依赖微管的封闭带的活跃破骨细胞中也能观察到。因此，足体带似乎让人联想到封闭带。事实上，足体带和封闭带的特点是它们的整体稳定性。尽管它们行为相似，但封闭带不是由足体融合形成的。足体带或封闭带的形成受外部环境控制。事实上，只有称为磷灰石晶体的骨矿物质部分能够诱导成熟破骨细胞形成封闭带。破骨细胞与磷灰石的接触会刺激非受体酪氨酸激酶c-Src和GTP酶Rho以形成封闭带。正如我们将在本综述中讨论的，足体和封闭带似乎有着惊人的联系。
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