Interferon-γ enhances the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects

Purpose: Interferon (IFN)-gamma is a major cytokine produced by immune cells that plays diverse roles in modulating both the immune system and bone metabolism, but its role in autogenous bone grafting remains unknown. Here, we present that local IFN-gamma-administration improved the efficacy of autogenous bone graft treatment in an experimental rat model. Methods: An autogenous bone graft model was prepared with critically sized rat calvariae defects. Four weeks (w) after bone graft implantation, rats were treated locally with IFN-gamma or were not treated. The effect of IFN-gamma on bone formation was evaluated for up to 8 w with micro-computed tomography, quantitative histomorphometry, and Von Kossa staining. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry staining or quantitative polymerase chain reactions were used to estimate the expression of osteoclast differentiation factor and inflammatory cytokines including tumor necrosis factor (TNF)-alpha, a well-known stimulant of osteoclastogenesis and an inhibitor of osteoblast activity, in defects. Results: Newly formed bone gradually replaced the autogenous bone grafts within 4 w, although severe bone resorption with osteoclastogenesis and TNF-alpha expression occurred after 6 w in the absence of IFN-gamma administration. IFN-gamma administration markedly attenuated bone loss, osteoclastogenesis, and TNF-alpha expression, while it enhanced bone formation at 8 w. Conclusion: Local IFN-gamma administration promoted bone formation in autogenous bone grafts possibly via regulating osteoclastogenesis and TNF-alpha expression. The data provide insights into the potential roles of IFN-gamma in autogenous bone grafting. (C) 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.