Yiming Zhang1,2, Xianqi Li3,4,5, Takahiro Chihara3, Hongwei Dong3, Hideaki Kagami6,7,8. 1. Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. zym811113@hotmail.com. 2. Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan. zym811113@hotmail.com. 3. Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan. 4. Department of Oral and Maxillofacial Surgery, School of Dentistry, Matsumoto Dental University, Shiojiri, Japan. 5. Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri, Nagano, 399-0781, Japan. 6. Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan. hideaki.kagami@mdu.ac.jp. 7. Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri, Nagano, 399-0781, Japan. hideaki.kagami@mdu.ac.jp. 8. Department of General Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. hideaki.kagami@mdu.ac.jp.
Abstract
BACKGROUND: Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs). METHODS: CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice. RESULTS: IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference. CONCLUSION: The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively.
BACKGROUND: Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs). METHODS: CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice. RESULTS: IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference. CONCLUSION: The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively.
Entities:
Keywords:
Apoptosis; Bone regeneration; Bone tissue engineering; IL-6; Osteoblasts; Osteogenic differentiation; TNF-α
Authors: Barbara Peruzzi; Alfredo Cappariello; Andrea Del Fattore; Nadia Rucci; Fabrizio De Benedetti; Anna Teti Journal: Nat Commun Date: 2012-01-17 Impact factor: 14.919