title: Synovial macrophage-osteoclast differentiation in inflammatory arthritis.
abstract: BACKGROUND
  Pathological bone resorption (marginal erosions and juxta-articular osteoporosis) by osteoclasts commonly occurs in rheumatoid arthritis (RA).
  
  
  OBJECTIVE
  To define the nature of the mononuclear precursor cells from which osteoclasts are formed in inflamed synovial tissues and to determine the cellular and humoral factors which influence osteoclast differentiation.
  
  
  METHODS
  Macrophage (CD14+), non-macrophage (CD14-), and unsorted (CD14+/CD14-) synovial cell populations from RA and inflammatory/non-inflammatory osteoarthritis (OA) synovium were cultured in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and monocyte-colony stimulating factor (M-CSF; in the presence/absence of prostaglandin E(2) (PGE(2)), interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), and IL6). Osteoclast differentiation was assessed by expression of tartrate resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar resorption.
  
  
  RESULTS
  TRAP+ and VNR+ multinucleated cells capable of lacunar resorption were only formed in cultures of CD14+-containing synovial cell populations (that is, CD14+ and CD14+/CD14- cells). No difference in the extent of osteoclast formation was noted in cultures of CD14+ cells isolated from RA, inflammatory OA, and non-inflammatory OA synovium. However, more TRAP+/VNR+ cells and more lacunar resorption was noted in CD14+/CD14- cells from RA and inflammatory OA synovial tissues. The addition of PGE(2), IL1beta, TNFalpha, and IL6 did not increase RANKL/M-CSF-induced osteoclast formation and lacunar resorption of both CD14+/CD14- and CD14+ synovial cell populations.
  
  
  CONCLUSIONS
  Osteoclast precursors in synovial tissues are CD14+ monocyte/macrophages. The increase in osteoclast formation in cultures of CD14+/CD14- compared with CD14+ synovial cells in RA and inflammatory OA points to a role for CD14- cells in promoting osteoclast differentiation and bone resorption in inflamed synovial tissues by a mechanism which does not involve a direct effect of proinflammatory cytokines/prostaglandins on RANKL-induced macrophage-osteoclast differentiation.
authors.affiliation: Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Danks
authors.forename: A
authors.initials: A
authors.lastname: Sabokbar
authors.forename: R
authors.initials: R
authors.lastname: Gundle
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000473:pathology*; D008297:Male; D010003:Osteoarthritis / Q000473:pathology*; D010010:Osteoclasts / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D015232:Dinoprostone