title: Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis.
abstract: OBJECTIVE
  In human osteoarthritis (OA), various forms of pathology are observed. Besides cartilage damage and fibrosis, neogenesis of bone, osteophyte formation, also occurs. Osteophytes are thought to limit joint movement and cause pain. The objective of this study was to investigate whether synovial macrophages are involved in osteophyte formation in experimental OA, and if they are, to study which mechanism may be involved.
  
  
  METHODS
  Experimental OA was induced by two intra-articular injections of collagenase on alternate days into murine knee joints. The role of synovial lining macrophages in this model was studied by selective removal of these cells prior to OA induction using clodronate liposomes. After 1 and 2 weeks, knee joints were dissected and examined (immuno)histologically.
  
  
  RESULTS
  At days 7 and 14 after induction of OA, osteophyte formation and fibrosis were observed. Depletion of synovial macrophages resulted in spectacular reduction of osteophyte formation, 84% and 66%, respectively, at days 7 and 14. Fibrosis and synovial activation, measured by MRP8/14 expression, were also ameliorated (40-60%). In addition, production of growth factors (TGFbeta, BMP-2 and BMP-4) in the lining was largely prevented but production of these growth factors in deeper layers of the synovium and the periosteum did not differ from controls.
  
  
  CONCLUSIONS
  These results indicate the synovial macrophage to be a pivotal cell in the synovium mediating osteophyte formation and other OA-related pathology, like fibrosis, during experimental OA. Production of growth factors and induction of synovial activation by these cells may play a crucial role in this event.
authors.affiliation: Experimental Arthritis and Advanced Therapies, University Medical Center Nijmegen, The Netherlands. a.blom@reuma.umcn.nl
authors.forename: Arjen B
authors.initials: AB
authors.lastname: Blom
authors.forename: Peter L E M
authors.initials: PL
authors.lastname: van Lent
authors.forename: Astrid E M
authors.initials: AE
authors.lastname: Holthuysen
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006133:Growth Substances / Q000096:biosynthesis; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
chemical_list: D006133:Growth Substances