IgG Immunocomplexes Drive the Differentiation of a Novel Subset of Osteoclasts Independent of RANKL and Inflammatory Cytokines.
J Bone Miner Res
; 36(6): 1174-1188, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33651383
ABSTRACT
Potentiation of receptor activator of NF-κB 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 FcγRIIa (hFcγRIIa) or co-ligating hFcγRIIa 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, hFcγRIIa-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 FcγR-mediated cartilage destruction from RANKL-related bone erosion in autoinflammatory arthritis. © 2021 American Society for Bone and Mineral Research (ASBMR)..
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Reabsorção Óssea
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Bone Miner Res
Assunto da revista:
METABOLISMO
/
ORTOPEDIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China