title: Interferon-γ enhances the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects.
abstract: OBJECTIVE
  Interferon (IFN)-γ 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-γ 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-γ or were not treated. The effect of IFN-γ on bone formation was evaluated for up to 8w 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)-α, 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 4w, although severe bone resorption with osteoclastogenesis and TNF-α expression occurred after 6w in the absence of IFN-γ administration. IFN-γ administration markedly attenuated bone loss, osteoclastogenesis, and TNF-α expression, while it enhanced bone formation at 8w.
  
  
  CONCLUSIONS
  Local IFN-γ administration promoted bone formation in autogenous bone grafts possibly via regulating osteoclastogenesis and TNF-α expression. The data provide insights into the potential roles of IFN-γ in autogenous bone grafting.
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Peiqi
authors: P
authors: Li
authors: Institute of Dental Research, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan. Electronic address: honda-y@cc.osaka-dent.ac.jp.
authors: Yoshitomo
authors: Y
authors: Honda
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Yoshiyuki
authors: Y
authors: Arima
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Kenichirou
authors: K
authors: Yasui
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Kaoru
authors: K
authors: Inami
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Aki
authors: A
authors: Nishiura
authors: Department of Biomaterials, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan. Electronic address: yoshiya@cc.osaka-dent.ac.jp.
authors: Yoshiya
authors: Y
authors: Hashimoto
authors: Department of Orthodontics, Osaka Dental University, 8-1, Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
authors: Naoyuki
authors: N
authors: Matsumoto
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D016025:Bone Transplantation; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012886:Skull; D013997:Time Factors; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Autogenous bone graft; Bone formation; Inflammation; Interferon-γ; Osteoclast