IgG promotes TNF‐α induced osteoclastogenesis by upregulating the expression of TNFR1 and the NF‐κB signalling pathway

Abstract Objectives Tumor necrosis factor‐α (TNF‐α) plays a pivotal role in bone damage associated with inflammatory arthritis such as rheumatoid arthritis (RA). Both systemic lupus erythematosus (SLE) and rheumatoid arthritis exhibit clinical manifestations of inflammatory arthritis, yet the joint...

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Bibliographic Details
Main Authors: Haifeng Yin, Yao Teng, Guo‐Min Deng
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Clinical & Translational Immunology
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Online Access:https://doi.org/10.1002/cti2.70034
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Summary:Abstract Objectives Tumor necrosis factor‐α (TNF‐α) plays a pivotal role in bone damage associated with inflammatory arthritis such as rheumatoid arthritis (RA). Both systemic lupus erythematosus (SLE) and rheumatoid arthritis exhibit clinical manifestations of inflammatory arthritis, yet the joint bone damage in RA is more severe than that in SLE. The reasons for this differential manifestation remain unclear. This study aimed to determine the role of IgG antibodies in TNF‐α‐induced osteoclastogenesis. Methods We conducted cellular experiments to ascertain whether IgG affects TNF‐α‐induced osteoclastogenesis and validate the role of IgG in TNF‐α‐induced cartilage destruction in mouse models of arthritis through animal studies. Results We found that IgG promoted TNF‐α‐induced osteoclastogenesis by upregulating the expression of tumor necrosis factor receptor 1 (TNFR1) and enhancing the downstream nuclear factor‐kappaB (NF‐κB) signalling pathway. In the TNF‐α‐induced arthritis mouse model, IgG further exacerbated the destruction of articular cartilage. Conclusion Our findings clarified that IgG aggravated TNF‐α‐mediated osteoclastogenesis, further elucidating the mechanistic basis for the divergent manifestations of joint bone damage in SLE and RA.
ISSN:2050-0068