期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 36, 期 6, 页码 1174-1188出版社
WILEY
DOI: 10.1002/jbmr.4281
关键词
IMMUNOCOMPLEX; FCGAMMA RECEPTOR IIa; NON‐ CLASSIC OSTEOCLAST; BONE EROSION; RHEUMATOID ARTHRITIS
资金
- Ministry of Science and Technology [2017YFA0104502]
- National Foundation of Natural Science [31770942]
- Priority Academic Program Development of Jiangsu Higher Education Institution (PARD) of China
The study demonstrates that IgG immunocomplexes can drive the differentiation of human blood monocytes into nonclassical osteoclasts independent of RANKL and inflammatory cytokines, and can also reverse classical osteoclast differentiation induced by RANKL in vitro. This finding may provide an explanation for the uncoupling of cartilage destruction and bone erosion in autoinflammatory arthritis.
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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