This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: [10.1002/jcb.24518].
Copyright © 2013 Wiley Periodicals, Inc.
Summary sentence: Inhibition of OC-STAMP, a membrane bound protein found in osteoclasts and foreign body giant cells, blocks the formation of multinuclear giant cells.
- Accepted manuscript online: 26 FEB 2013 08:37AM EST
- Manuscript Accepted: 12 FEB 2013
- Manuscript Revised: 7 FEB 2013
- Manuscript Received: 19 OCT 2012
- Cited By
- multinuclear giant cells
Macrophages have the ability to fuse and form multinucleated giant cells such as osteoclasts (OCs) and foreign body giant cells (FBGCs). Osteoclast stimulatory transmembrane protein (OC-STAMP) is an important cell surface protein involved in the formation of osteoclasts. This study sought to determine if OC-STAMP also regulates formation of FBGCs using expression analysis and subsequent inhibition studies. qPCR and Western blot analysis showed that OC-STAMP expression is significantly higher in FBGCs compared to control monocytes (P < 0.05). Four days following cell culture, OCs were positive for TRAP and F-actin ring formation, but FBGCs were not. In contrast, FBGCs were positive for TRAP and showed podosome belts comprised of F-actin on day eight. FBGCs were subsequently plated onto dentine, but despite presenting some morphologic features of OCs (OC-STAMP expression, TRAP reactivity and podosome belts) they failed to resorb bone. To evaluate a role for OC-STAMP in FBGCs, we inhibited this cell surface protein with anti-OC-STAMP antibody and observed that cell fusion and podosome belt formation was inhibited in both OCs and FBGCs. Our data support the hypothesis that OC-STAMP is a regulatory molecule for FBGCs; and that they are functionally distinct from OCs, despite similarities in gene expression profile, podosome belt formation and TRAP expression. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.