Titania nanotubes promote osteogenesis via mediating crosstalk between macrophages and MSCs under oxidative stress

Colloids Surf B Biointerfaces. 2019 Aug 1:180:39-48. doi: 10.1016/j.colsurfb.2019.04.033. Epub 2019 Apr 18.

Abstract

Before mesenchymal stem cells (MSCs) adhere to the surface of an implant and differentiate into osteoblasts, monocytes (especially macrophages) arrive at the bone injury site and interact with the implant and subsequent MSCs. In our previous study, large titania nanotubes (TNT110) had been verified to endow superior oxidation resistance to osteoblasts. The early regulation between macrophages and MSCs by surface nanotubes under oxidative stress (OS) was evaluated further in this study. Cellular and molecular results show that TNT110 greatly increased early inflammation of macrophages by activating integrin/FAK-mediated MAPK and NFκB signals and simultaneously promoted their gene expression of SDF1, IL-8, and CCL2 (chemokines) compared with 30 nm nanotubes and titanium substrates. Co-culture results show that more MSCs were recruited by those chemokines and may promote osteogenic self-differentiation, reducing early inflammation of macrophages by accelerating their M1-to-M2 transition in the TNT110 group. All findings reveal that the early cellular behavior of macrophages and MSCs was effectively regulated by TNT110, indicating large nanotubes would be more suitable to prevent oxidative damages.

Keywords: Inflammation; Molecular mechanism; Osteogenesis; Oxidative stress; Titania nanotubes.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Communication / drug effects*
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Coculture Techniques
  • Gene Expression Regulation / drug effects
  • Integrins / genetics
  • Integrins / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Nitric Oxide / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Oxidative Stress / drug effects
  • RAW 264.7 Cells
  • Signal Transduction
  • Titanium / pharmacology*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • IL10 protein, mouse
  • Integrins
  • Interleukin-8
  • Rela protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • titanium dioxide
  • Nitric Oxide
  • Titanium