Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength.
Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength.
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DOI：
10.1083/jcb.148.4.665
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发表时间：
2000-02-21
期刊：
影响因子：
--
通讯作者：
Hruska KA
中科院分区：
文献类型：
--
作者：
Chellaiah M;Kizer N;Silva M;Alvarez U;Kwiatkowski D;Hruska KA
破骨细胞是一种独特的细胞，它在运动过程中利用足体而不是局部粘连来附着基质和重塑细胞骨架。我们已经证明，骨桥蛋白(OP)与破骨细胞足体的αvβ3整合素结合，通过激活包括明胶蛋白、pp60c-src和磷脂酰肌醇3‘-激酶在内的异构体信号复合体，刺激细胞骨架重组和骨吸收。在这里，我们证明了明胶蛋白缺乏阻止了足体组装和αvβ3刺激的与明胶蛋白缺失小鼠的运动相关的信号。明胶蛋白缺乏的破骨细胞由于肌动蛋白细胞骨架的重塑迟缓而运动迟缓。它们不能通过刺激运动和骨吸收来对自分泌因子OP作出反应。明胶蛋白缺乏与正常的骨骼发育和软骨内骨生长有关。然而，明胶蛋白缺失的小鼠有轻度的骨骺结构异常，干骺端小梁中保留了软骨蛋白多糖，小梁厚度增加。随着年龄的增长，明胶蛋白缺乏的小鼠表现出骨小梁和皮质骨厚度的增加，从而产生机械性能更强的骨骼。这些观察结果表明，明胶蛋白通过αvβ3整合素在足体组装、快速细胞运动和信号转导中发挥关键作用。
Osteoclasts are unique cells that utilize podosomes instead of focal adhesions for matrix attachment and cytoskeletal remodeling during motility. We have shown that osteopontin (OP) binding to the αvβ3 integrin of osteoclast podosomes stimulated cytoskeletal reorganization and bone resorption by activating a heteromultimeric signaling complex that includes gelsolin, pp60c-src, and phosphatidylinositol 3′-kinase. Here we demonstrate that gelsolin deficiency blocks podosome assembly and αvβ3-stimulated signaling related to motility in gelsolin-null mice. Gelsolin-deficient osteoclasts were hypomotile due to retarded remodeling of the actin cytoskeleton. They failed to respond to the autocrine factor, OP, with stimulation of motility and bone resorption. Gelsolin deficiency was associated with normal skeletal development and endochondral bone growth. However, gelsolin-null mice had mildly abnormal epiphyseal structure, retained cartilage proteoglycans in metaphyseal trabeculae, and increased trabecular thickness. With age, the gelsolin-deficient mice expressed increased trabecular and cortical bone thickness producing mechanically stronger bones. These observations demonstrate the critical role of gelsolin in podosome assembly, rapid cell movements, and signal transduction through the αvβ3 integrin.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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