Immune complex-induced inhibition of osteoclastogenesis is mediated via activating but not inhibitory Fcgamma receptors on myeloid precursor cells
SourceAnnals of the Rheumatic Diseases, 72, 2, (2013), pp. 278-85
Article / Letter to editor
Display more detailsDisplay less details
Annals of the Rheumatic Diseases
SubjectNCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapy
OBJECTIVE: To investigate the role of Fcgamma receptors (FcgammaRs) in osteoclastogenesis and osteoclast function. METHODS: Bone destruction was analysed in arthritic knee joints of several FcgammaR-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 alpha (TNFalpha) or lipopolysaccharide (LPS). In addition, mature osteoclasts were stimulated with ICs. Experiments were analysed for osteoclast formation, bone resorption and the expression of FcgammaRs and osteoclast markers. RESULTS: Bone destruction was significantly increased in arthritic knee joints of FcgammaRIIB-deficient mice. All FcgammaR classes were highly expressed on osteoclast precursors. Expression of the inhibitory FcgammaRIIB was similar on mature osteoclasts compared to macrophages, whereas activating FcgammaR 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 FcgammaRIIB(-/-) precursors and bone resorption remained inhibited. In contrast, ICs could not inhibit osteoclast formation or bone resorption of FcRgamma-chain(-/-) precursors. When IC-inhibited osteoclastogenesis was followed by stimulation with TNFalpha or LPS, the inhibitory effects of ICs were overruled. CONCLUSION: Activating FcgammaRs mediate IC-induced inhibition of osteoclastogenesis, which might be overruled in the presence of proinflammatory mediators. This suggests that the balance of FcgammaR-mediated inflammation, through proinflammatory cytokine production, as well as the direct inhibitory effect of ICs on osteoclastogenesis determines the net effect on bone loss.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.