|Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
|Year of Publication
|Sakunrangsit N, Metheepakornchai P, Kumpunya S, Greenblatt MBlake, Leelahavanichkul A, Pisitkun P, Lotinun S
|Alveolar Bone Loss, Animals, Bone and Bones, Bone Diseases, Metabolic, Disease Models, Animal, Etanercept, Inflammation, Lupus Erythematosus, Systemic, Male, Mandible, Mandibular Diseases, Mice, Mice, Knockout, Osteoblasts, Osteoclasts, Periodontitis, Receptors, IgG, Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor-alpha
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-α antagonist could prevent mandibular bone loss in the FcγRIIb-/- mouse model of lupus. Mice lacking FcγRIIb 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 FcγRIIb-deficient mice. FcγRIIb 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 FcγRIIb-/- mice. Osteoclast marker genes including TNF-α, Trap and RANKL/OPG ratio was decreased in WT. Serum markers of proinflammatory cytokines, TNF-α, IFNγ, IL-6, and IL-17A, were increased in FcγRIIb-/- mice and etanercept antagonized these effects in FcγRIIb-/- mice. Etanercept increased serum PTH levels in the FcγRIIb-/- mouse model of lupus. Our results suggest that deletion of FcγRIIb induces osteopenia by increasing the level of proinflammatory cytokines. Etanercept is effective in preventing mandibular bone loss in FcγRIIb-/- mice, suggesting that anti-TNF-α therapy may be able to ameliorate mandibular bone loss in SLE patients with periodontitis.
|PubMed Central ID
Matthew B. Greenblatt, M.D., Ph.D.