Igg Immunocomplexes Drive The Differentiation Of A Novel Subset Of Osteoclasts Independent Of Rankl And Inflammatory Cytokines
JOURNAL OF BONE AND MINERAL RESEARCH(2021)
摘要
Potentiation of receptor activator of NF-kappa B ligand (RANKL)-induced osteoclastogenesis by IgG immunocomplexes (ICs) is generally considered an important pathway leading to cartilage and bone destruction in rheumatoid arthritis (RA). However, whether IgG ICs possess pro-osteoclastogenic potential independent of RANKL and inflammatory cytokines is unclear. Here we demonstrate that by fully cross-linking human Fc gamma RIIa (hFc gamma RIIa) or co-ligating hFc gamma RIIa and TLR4, IgG ICs alone could drive the differentiation of human blood monocytes into nuclear factor of activated T cells cytoplasmic 1 (NFATc1-negative nonclassical osteoclasts (NOCs). Surprisingly, IgG ICs could also overrule RANKL-induced classical osteoclast (COC) differentiation in vitro. In mouse model of collagen-induced arthritis, hFc gamma RIIa-transgenic, but not nontransgenic control, mice suffered from cartilage/bone destruction accompanied by the presence of NFATc1(-) NOCs lining the eroded cartilage surface in affected joints. Our results not only identify a novel subset of IC-induced NOCs but also provide a possible explanation for the uncoupling of Fc gamma R-mediated cartilage destruction from RANKL-related bone erosion in autoinflammatory arthritis. (c) 2021 American Society for Bone and Mineral Research (ASBMR)..
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关键词
IMMUNOCOMPLEX, FCGAMMA RECEPTOR IIa, NON‐, CLASSIC OSTEOCLAST, BONE EROSION, RHEUMATOID ARTHRITIS
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