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Effect of TNF-α and IL-6 on Compact Bone-Derived Cells

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Tissue Engineering and Regenerative Medicine Aims and scope

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.

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Authors and Affiliations

  1. Department of Stomatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China

    Yiming Zhang

  2. Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan

    Yiming Zhang, Xianqi Li, Takahiro Chihara, Hongwei Dong & Hideaki Kagami

  3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Matsumoto Dental University, Shiojiri, Japan

    Xianqi Li

  4. Institute for Oral Science, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri, Nagano, 399-0781, Japan

    Xianqi Li & Hideaki Kagami

  5. Department of General Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Hideaki Kagami

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  1. Yiming Zhang
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  3. Takahiro Chihara
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Correspondence to Yiming Zhang or Hideaki Kagami.

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Ethical statement

Animal care and experimental procedures were carried out in accordance with the approval of the ‘‘Matsumoto Dental University Committee on Intramural Animal Use’’ (No. 228).

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Zhang, Y., Li, X., Chihara, T. et al. Effect of TNF-α and IL-6 on Compact Bone-Derived Cells. Tissue Eng Regen Med 18, 441–451 (2021). https://doi.org/10.1007/s13770-021-00336-1

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  • DOI: https://doi.org/10.1007/s13770-021-00336-1

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