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- Title
IgG Immunocomplexes Drive the Differentiation of a Novel Subset of Osteoclasts Independent of RANKL and Inflammatory Cytokines.
- Authors
Zeng, Ke‐Qin; Gong, Fang‐Yuan; Pan, Xiao‐Hua; Miao, Jie; Gong, Zheng; Wang, Jun; Zhong, Qiao; Dai, Xia‐Qiu; Gao, Xiao‐Ming
- 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)..
- Subjects
TRANCE protein; OSTEOCLASTOGENESIS; OSTEOCLASTS; LABORATORY mice; MONOCYTES; BONE resorption; COLLAGEN-induced arthritis; CYTOKINES
- Publication
Journal of Bone & Mineral Research, 2021, Vol 36, Issue 6, p1174
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.4281