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

Abstract

Purpose: Interferon (IFN)-g 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 autoge- nous bone grafting remains unknown. Here, we present that local IFN-g 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-g or were not treated. The effect of IFN-g 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. Immuno- histochemistry staining or quantitative polymerase chain reactions were used to estimate the expression of osteoclast differentiation factor and inflammatory cytokines including tumor necrosis factor (TNF)-a, a well-known stimulant of osteoclastogenesis and an inhibi- tor 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-a expression occurred after 6 w in the absence of IFN-g administration. IFN-g administration markedly attenuated bone loss, osteoclastogenesis, and TNF-a expression, while it enhanced bone formation at 8 w. Conclusion: Local IFN-g administration promoted bone formation in autogenous bone grafts possibly via regulating osteoclastogenesis and TNF-a expression. The data provide insights into the potential roles of IFN-g in autogenous bone grafting.