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

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-alpha) on differentiation and apoptosis of compact bone-derived cells (CBDCs). Methods: CBDCs were obtained from mouse legs and cultured. The effects of TNF-alpha 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-alpha 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-alpha, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-alpha 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-alpha 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.

Automated summary

This study highlights the important role of IL-6 in modulating the efficacy of bone tissue engineering, showing both positive and negative effects on CBDCs. TNF-alpha, on the other hand, significantly suppresses the expression of osteogenic markers. In vivo experiments demonstrate a correlation between high IL-6 expression and new bone formation, while TNF-alpha expression does not show notable differences.