Chellaiah M A, Hruska K A
Department of Oral & Craniofacial Biological Sciences, University of Maryland, Baltimore, MD 21201, USA.
Calcif Tissue Int. 2003 Mar;72(3):197-205. doi: 10.1007/s00223-002-1025-6. Epub 2002 Dec 10.
In the studies reported here we demonstrate that osteopontin is secreted from the basolateral surfaces of osteoclasts where it binds to the avb3-integrin, suggesting that it may be an autocrine factor. Osteopontin stimulation of osteoclasts produced changes in cell shape by causing disruption of peripheral podosome structures and formation of actin filaments at the leading edge of the migrating osteoclasts. The latter was part of the assumption of a motile phenotype prior to cells reforming peripheral ring type podosome containing clear zones. It is well established in our laboratory as well as in others that osteopontin stimulated osteoclast motility and bone resorption. The effect of osteopontin was mimicked by RGD containing peptides and blocked by a avb3 antibody, demonstrating that signals generated by integrin ligation contributed to the actions of osteopontin. In addition, the migratory effects of osteopontin on osteoclasts were also mediated through CD44 receptors since blocking antibodies to CD44 blocked stimulation of motility. Our data strongly suggest that osteopontin is an osteoclast autocrine motility factor binding to avb3 and CD44 during stimulation of osteoclast migration.
在本文报道的研究中，我们证明骨桥蛋白是从破骨细胞的基底外侧表面分泌的，在那里它与αvβ3整合素结合，这表明它可能是一种自分泌因子。骨桥蛋白对破骨细胞的刺激通过破坏外周足体结构并在迁移的破骨细胞前缘形成肌动蛋白丝而导致细胞形态发生变化。后者是细胞形成含透明区的外周环状足体之前呈现运动表型的一部分。在我们实验室以及其他实验室中都已充分证实，骨桥蛋白可刺激破骨细胞的运动性和骨吸收。含RGD的肽可模拟骨桥蛋白的作用，而αvβ3抗体可阻断其作用，这表明整合素连接产生的信号有助于骨桥蛋白的作用。此外，骨桥蛋白对破骨细胞的迁移作用也通过CD44受体介导，因为抗CD44的阻断抗体可阻断对运动性的刺激。我们的数据有力地表明，骨桥蛋白是一种破骨细胞自分泌运动因子，在刺激破骨细胞迁移过程中与αvβ3和CD44结合。
