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Immune complex-induced inhibition of osteoclastogenesis is mediated via activating but not inhibitory Fcγ receptors on myeloid precursor cells
  1. Lilyanne C Grevers1,
  2. Teun J de Vries2,
  3. Vincent Everts2,
  4. J Sjef Verbeek3,
  5. Wim B van den Berg1,
  6. Peter L E M van Lent1
  1. 1Department of Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2Departments of Periodontology and Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam, VU University Amsterdam, and Research Institute MOVE, Amsterdam, The Netherlands
  3. 3Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Lilyanne Catharine Grevers, Department of Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 272, Nijmegen 6525 GA, The Netherlands; LGrevers{at}


Objective To investigate the role of Fcγ receptors (FcγRs) in osteoclastogenesis and osteoclast function.

Methods Bone destruction was analysed in arthritic knee joints of several FcγR-knockout mouse strains. Unfractionated bone marrow cells were differentiated in vitro towards osteoclasts in the absence or presence of immune complexes (ICs) and stimulated thereafter for 24 h with tumour necrosis factor α (TNFα) or lipopolysaccharide (LPS). In addition, mature osteoclasts were stimulated with ICs. Experiments were analysed for osteoclast formation, bone resorption and the expression of FcγRs and osteoclast markers.

Results Bone destruction was significantly increased in arthritic knee joints of FcγRIIB-deficient mice. All FcγR classes were highly expressed on osteoclast precursors. Expression of the inhibitory FcγRIIB was similar on mature osteoclasts compared to macrophages, whereas activating FcγR levels were significantly lower. IC stimulation of mature osteoclasts did not affect their number or their bone resorptive capacity. ICs significantly inhibited differentiation of unfractionated bone marrow cells towards osteoclasts, bone resorption and expression of osteoclast markers. In the presence of ICs, osteoclastogenesis of FcγRIIB−/− precursors and bone resorption remained inhibited. In contrast, ICs could not inhibit osteoclast formation or bone resorption of FcRγ-chain−/− precursors. When IC-inhibited osteoclastogenesis was followed by stimulation with TNFα or LPS, the inhibitory effects of ICs were overruled.

Conclusion Activating FcγRs mediate IC-induced inhibition of osteoclastogenesis, which might be overruled in the presence of proinflammatory mediators. This suggests that the balance of FcγR-mediated inflammation, through proinflammatory cytokine production, as well as the direct inhibitory effect of ICs on osteoclastogenesis determines the net effect on bone loss.

  • Rheumatoid Arthritis
  • Inflammation
  • Autoimmune Diseases
  • Autoantibodies

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