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Publication : Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.

First Author  Sakunrangsit N Year  2021
Journal  PLoS One Volume  16
Issue  4 Pages  e0250215
PubMed ID  33861790 Mgi Jnum  J:305397
Mgi Id  MGI:6696001 Doi  10.1371/journal.pone.0250215
Citation  Sakunrangsit N, et al. (2021) Etanercept prevents TNF-alpha mediated mandibular bone loss in FcgammaRIIb-/- lupus model. PLoS One 16(4):e0250215
abstractText  Patients with systemic lupus erythematosus are at increased risk for alveolar bone loss due to periodontitis possibly as a result of a pathogenic immune response to oral bacteria and inflammation. The aim of the present study was to investigate whether an anti-TNF-alpha antagonist could prevent mandibular bone loss in the FcgammaRIIb-/- mouse model of lupus. Mice lacking FcgammaRIIb had decreased cancellous and cortical bone volume at 6 months of age. Etanercept increased cancellous but not cortical bone volume in WT and increased both cancellous bone volume and cortical thickness in FcgammaRIIb-deficient mice. FcgammaRIIb deficiency decreased mRNA levels for osteoblast marker genes, Osx, Col1a1 and Alp without any change in osteoclast marker genes. Etanercept increased Osx, Alp, and Ocn in both WT and FcgammaRIIb-/- mice. Osteoclast marker genes including TNF-alpha, Trap and RANKL/OPG ratio was decreased in WT. Serum markers of proinflammatory cytokines, TNF-alpha, IFNgamma, IL-6, and IL-17A, were increased in FcgammaRIIb-/- mice and etanercept antagonized these effects in FcgammaRIIb-/- mice. Etanercept increased serum PTH levels in the FcgammaRIIb-/- mouse model of lupus. Our results suggest that deletion of FcgammaRIIb induces osteopenia by increasing the level of proinflammatory cytokines. Etanercept is effective in preventing mandibular bone loss in FcgammaRIIb-/- mice, suggesting that anti-TNF-alpha therapy may be able to ameliorate mandibular bone loss in SLE patients with periodontitis.
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