title: Surface-associated protein from Staphylococcus aureus stimulates osteoclastogenesis: possible role in S. aureus-induced bone pathology.
abstract: OBJECTIVE
  Staphylococcus aureus is the cause of bone destruction in osteomyelitis, bacterial arthritis and orthopaedic implant failure. We have previously shown that gentle saline extraction of S. aureus has revealed the presence of an extremely potent stimulator of osteoclast activation in both the murine calvarial bone resorption assay and the isolated chick osteoclast resorption assay. In order to investigate the mechanism of action of this surface-associated material (SAM), we have investigated its capacity to recruit osteoclasts.
  
  
  METHODS
  The murine bone marrow osteoclast recruitment assay was used. The ability of the recruited cells to resorb dentine slices was also investigated. Results. The SAM from S. aureus dose dependently stimulated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and pit formation on dentine slices. Neutralization of the cytokines tumour necrosis factor alpha and interleukin (IL)-6 totally inhibited, but antagonism of IL-1 only partially blocked, the stimulated maturation of osteoclast-like cells.
  
  
  CONCLUSIONS
  These findings suggest that bone destruction associated with local infection by S. aureus is due to the stimulation of osteoclast formation induced by the action of the easily solubilized SAM, and could explain the large numbers of osteoclasts found in infarcted bone in osteomyelitis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Eastman Dental Institute for Oral Health Care Sciences, London.
authors.forename: S
authors.initials: S
authors.lastname: Meghji
authors.forename: S J
authors.initials: SJ
authors.lastname: Crean
authors.forename: P A
authors.initials: PA
authors.lastname: Hill
authors.forename: M
authors.initials: M
authors.lastname: Sheikh
authors.forename: S P
authors.initials: SP
authors.lastname: Nair
authors.forename: K
authors.initials: K
authors.lastname: Heron
authors.forename: B
authors.initials: B
authors.lastname: Henderson
authors.forename: E B
authors.initials: EB
authors.lastname: Mawer
authors.forename: M
authors.initials: M
authors.lastname: Harris
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D003804:Dentin / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D015726:Giant Cells / Q000187:drug effects / Q000201:enzymology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009500:Neutralization Tests; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013211:Staphylococcus aureus; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D002116:Calcitonin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D007213:Indomethacin