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Bone Is Not Essential for Osteoclast Activation.

Fuller, K; Ross, JL; Szewczyk, KA; Moss, R; Chambers, TJ (2010) Bone Is Not Essential for Osteoclast Activation. PLOS ONE, 5 (9). e12837 - e12837 (14). ISSN 1932-6203
SGUL Authors: Chambers, Timothy John

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Background: The mechanism whereby bone activates resorptive behavior in osteoclasts, the cells that resorb bone, is unknown. It is known that avb3 ligands are important, because blockade of avb3 receptor signaling inhibits bone resorption, but this might be through inhibition of adhesion or migration rather than resorption itself. Nor is it known whether avb3 ligands are sufficient for resorption the consensus is that bone mineral is essential for the recognition of bone as the substrate appropriate for resorption. Methodology/Principal Findings: Vitronectin- but not fibronectin-coated coverslips induced murine osteoclasts to secrete tartrate-resistant acid phosphatase, as they do on bone. Osteoclasts incubated on vitronectin, unlike fibronectin, formed podosome belts on glass coverslips, and these were modulated by resorption-regulating cytokines. Podosome belts formed on vitronectin-coated surfaces whether the substrates were rough or smooth, rigid or flexible. We developed a novel approach whereby the substrate-apposed surface of cells can be visualized in the scanning electron microscope. With this approach, supported by transmission electron microscopy, we found that osteoclasts on vitronectin-coated surfaces show ruffled borders and clear zones characteristic of resorbing osteoclasts. Ruffles were obscured by a film if cells were incubated in the cathepsin inhibitor E64, suggesting that removal of the film represents substrate-degrading behavior. Analogously, osteoclasts formed resorption-like trails on vitronectin-coated substrates. Like bone resorption, these trails were dependent upon resorbogenic cytokines and were inhibited by E64. Bone mineral induced actin rings and surface excavation only if first coated with vitronectin. Fibronectin could not substitute in any of these activities, despite enabling adhesion and cell spreading. Conclusions/Significance: Our results show that ligands avb3 are not only necessary but sufficient for the induction of resorptive behavior in osteoclasts; and suggest that bone is recognized through its affinity for these ligands, rather than by its mechanical or topographical attributes, or through a putative ‘mineral receptor’.

Item Type: Article
Additional Information: Copyright: © 2010 Fuller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Acid Phosphatase, Animals, Bone Resorption, Bone and Bones, Cells, Cultured, Isoenzymes, Mice, Osteoclasts, Vitronectin, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ISOLATED RABBIT OSTEOCLASTS, VITRONECTIN RECEPTOR, SEALING ZONE, IN-VITRO, CYTOSKELETAL ORGANIZATION, ALPHA(V)BETA(3) INTEGRIN, RESORBING OSTEOCLASTS, CULTURED OSTEOCLASTS, EXTRACELLULAR-MATRIX, PARATHYROID-HORMONE
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
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17 September 2010Published
Web of Science ID: WOS:000281960800025
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