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Synovial macrophage-osteoclast differentiation in inflammatory arthritis
  1. L Danks1,
  2. A Sabokbar1,
  3. R Gundle1,
  4. N A Athanasou2
  1. 1Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK
  2. 2Department of Pathology, Nuffield Orthopaedic Centre, Oxford, UK
  1. Correspondence to:
    Dr N A Athanasou, Department of Pathology, Nuffield Orthopaedic Centre, Windmill Road Headington, Oxford, OX3 7LD, UK;


Background: Pathological bone resorption (marginal erosions and juxta-articular osteoporosis) by osteoclasts commonly occurs in rheumatoid arthritis (RA).

Objectives: 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.

Method: 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 κB ligand (RANKL) and monocyte-colony stimulating factor (M-CSF; in the presence/absence of prostaglandin E2 (PGE2), interleukin 1β (IL1β), tumour necrosis factor α (TNFα), 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 PGE2, IL1β, TNFα, 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.

  • osteoclast
  • synovial macrophages
  • bone resorption
  • arthritis
  • Dex, dexamethasone
  • FCS, fetal calf serum
  • IL, interleukin
  • M-CSF, macrophage-colony stimulating factor
  • αMEM, alpha minimum essential medium
  • OA, osteoarthritis
  • OPG, osteoprotegerin
  • PGE2, prostaglandin E2
  • RA, rheumatoid arthritis
  • RANK, receptor activator for nuclear factor κB
  • RANKL, RANK ligand
  • sIL6R, soluble interleukin 6 receptor
  • TNFα, tumour necrosis factor α
  • TRAP, tartrate resistant acid phosphatase
  • VNR, vitronectin receptor
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