title: Foreign body giant cells and osteoclasts are TRAP positive, have podosome-belts and both require OC-STAMP for cell fusion.
abstract: Macrophages have the ability to fuse and form multinucleated giant cells such as Osteoclast (OCs) and FBGCs. Osteoclast stimulatory transmembrane protein (OC-STAMP) is an important cell surface protein involved in the formation of OCs. 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 8. 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.
authors: School of Medical Science, Griffith University, Gold Coast, QLD 4215, Australia.
authors: Usman A
authors: UA
authors: Khan
authors: Saeed M
authors: SM
authors: Hashimi
authors: Mahmoud M
authors: MM
authors: Bakr
authors: Mark R
authors: MR
authors: Forwood
authors: Nigel A
authors: NA
authors: Morrison
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002459:Cell Fusion; D021961:Cell Membrane Structures / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D015743:Giant Cells, Foreign-Body / Q000166:cytology / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
chemical_list: D000199:Actins; D007527:Isoenzymes; D008565:Membrane Proteins; C527519:OC-STAMP protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase