期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7651
关键词
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资金
- Deutsche Forschungsgemeinschaft (Focus program) [SPP1468]
- Bundesministerium fur Bildung und Forschung (BMBF
- METARTHROS)
- Marie-Curie project Osteoimmune
- TEAM
- Masterswitch project of the European Union
- IMI funded project BTCure
- Interdisciplinary Centre for Clinical Research of the University of Erlangen-Nuremberg
- Deutsche Forschungsgemeinschaft [GK1660]
- Dutch Arthritis Foundation
- Netherlands Organization for Health Research and Development
- ReumaFonds [12-2-403] Funding Source: researchfish
Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fc gamma receptors (Fc gamma R) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.
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