Abstract
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.
Highlights
Periodontitis is a chronic inflammation and destruction of periodontal tissue leading to mandibular alveolar bone loss induced by osteoclasts
Deletion of FcγRIIb induced osteopenia in the mandible by 6 months of age Previous studies indicated that FcγRIIb-/- mice developed spontaneous systemic lupus erythematosus (SLE) at 6 months of age
To evaluate whether the absence of FcγRIIb affected mandibular cancellous and cortical bone in 3-monthold mice, μCT analysis was performed. μCT analysis showed no difference in cancellous bone volume, trabecular thickness, structure model index (SMI), and bone mineral density (BMD) (Fig 1A and 1B)
Summary
Periodontitis is a chronic inflammation and destruction of periodontal tissue leading to mandibular alveolar bone loss induced by osteoclasts. Gram-negative bacteria, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were identified as major periodontal pathogens [1]. They produce virulence factors that disturb host-microbe homeostasis. Anti-TNF-α prevents mandibular bone loss in lupus mice inflammation and over activation of the host immune response which stimulates osteoclast activity leading to alveolar bone loss [2]. Myeloid cells including monocytes and macrophages may be responsible for collateral damage to the periodontal tissues. Phagocytosis of pathogenic microorganisms by myeloid cell populations leads to the penetration of bacteria into periodontal tissue [3]
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