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THU0053 FC Gamma Receptors Enhance Bone Erosion in Experimental Arthritis by Stimulating Synovial Inflammation and Activation of Osteoclasts
  1. I. Di Ceglie1,
  2. S. Verbeek2,
  3. P. van der Kraan1,
  4. W. van den Berg1,
  5. P. van Lent1
  1. 1Experimental Rheumatology, Radboud University Medical Center, Nijmegen
  2. 2Human Genetics, Leiden University Medical Center, Leiden, Netherlands


Background Rheumatoid arthritis is characterized by immune complex dependent chronic joint inflammation and severe cartilage and bone destruction. In earlier studies we showed that Fcγ receptors (FcγRs) are crucial in regulating cartilage destruction during immune complex mediated antigen induced arthritis (AIA)(1,2). In this study we investigated the role of FcγRs in osteoclast-mediated bone erosion comparing development of AIA between mice lacking all FcγRs (FcγRI,II,III,IV -/-) and their wild type controls.

Objectives To investigate the role of FcγRs in bone erosion in AIA.

Methods AIA was induced by injection of 60 μg mBSA into the knee joint of FcγRI,II,III,IV-/- and wild type (WT) control mice previously immunized with mBSA/CFA. Joint inflammation and bone destruction were determined in total knee joints sections. mBSA antibody titers were measured using ELISA and T cell response was monitored with a lymphocyte stimulation test. The percentage of osteoclast precursors in the bone marrow was defined through FACS analysis. Gene expression was measured using RT-PCR. Mature osteoclasts within the knee joint were visualized with TRAP staining and counted in the locations of bone erosion in the patella, femur and tibia.

Results In FcγRI,II,III,IV -/- mice the development of bone erosion in knee joints was significantly reduced both at days 7 and 21 after induction of AIA (30% and 25% lower) when compared to WT controls. The immune response against mBSA (serum level of specific anti mBSA (total IgG, IgG1, IgG2b) and mBSA specific T-cell response) was comparable between the two strains. The percentage of osteoclast precursor population within the bone marrow (CD11b low-neg/ Ly6C high, described to be upregulated during arthritis) was comparable between FcγRI,II,III,IV -/- and WT controls. Moreover FcγRI,II,III,IV -/- and WT bone marrow cells showed the same ability to differentiate into osteoclasts upon stimulation with M-CSF and RANK-L in vitro. At day 7 after AIA induction, the decrease in bone erosion in FcγRI,II,III,IV -/- was associated with a significantly decrease in the number of inflammatory cells present within the joint (infiltrate and exudate 29% and 27% lower respectively compared to WT control). Interestingly no differences were present in the number of mature osteoclasts present at locations of bone erosion within the knee join (32±13 osteoclasts/ total knee joint section in FcγRI,II,II,IV-/- versus 28±9 osteoclasts/ total knee joint section in WT). Gene expression of osteoclast activation factors (RANK-L, IL-1β, S100A8) within the synovium was however significantly lower in FcγRI,II,III,IV-/- (ddCt -2.7, -2.6, -3, respectively) suggesting that FcγRs may drive osteoclast activation.

Conclusions FcγRs promote bone erosion in AIA not by increasing the number of osteoclasts present on the bone surface but by enhancing influx and activation of inflammatory cells within the synovium thereby releasing factors able to stimulate osteoclast activity.


  1. van Lent PL et al., Am J Pathol. 2001

  2. van Lent PL et al., Arthritis Rheum., 2010

Disclosure of Interest None declared

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