| First Author | Grötsch B | Year | 2019 |
| Journal | J Bone Miner Res | Volume | 34 |
| Issue | 7 | Pages | 1352-1365 |
| PubMed ID | 30779858 | Mgi Jnum | J:294972 |
| Mgi Id | MGI:6458229 | Doi | 10.1002/jbmr.3705 |
| Citation | Grotsch B, et al. (2019) Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss. J Bone Miner Res 34(7):1352-1365 |
| abstractText | Next to proinflammatory cytokines, autoimmunity has been identified as a key trigger for osteoclast activation and bone loss. IgG-rheumatoid factor (IgG-RF) immune complexes, which are present in patients with rheumatoid arthritis, were shown to boost osteoclast differentiation. To date, the regulation of IgG-RF production in the absence of inflammatory triggers is unknown. Herein, we describe Fra1 as a key checkpoint that controls IgG-RF production by plasma cells and regulates autoimmune-mediated bone loss. Fra1 deficiency in B cells (Fra1(DeltaBcell) ) led to increased IgG1-producing bone marrow plasma cells, enhanced IgG-RF production, and increased bone loss associated with elevated osteoclast numbers after immunization. The effect of IgG-RF on osteoclasts in vitro and on osteoclasts associated with bone loss in vivo was dependent on FcgammaR, especially FcgammaR3. Furthermore, immunization of WT mice with T-cell-dependent antigens induced a significant and robust decrease in Fra1 expression in bone marrow B cells, which was followed by increased IgG1 production and the induction of osteoclast-mediated bone loss. Overall, these data identify Fra1 as a key mediator of IgG-RF production and autoimmune-mediated bone loss. (c) 2019 American Society for Bone and Mineral Research. |
