Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

J Nanobiotechnology. 2020 Feb 18;18(1):33. doi: 10.1186/s12951-020-00590-w.

Abstract

Background: Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis.

Results: The α-Fe2O3/γ-Fe2O3 nanocomposite (IOs) was prepared using the modified sol-gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts.

Conclusion: Fabricated by our group α-Fe2O3/γ-Fe2O3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.

Keywords: Iron oxides; Osteoblasts; Osteoclasts; Osteoporosis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cellular Microenvironment / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Integrin alpha3 / genetics
  • Integrin alpha3 / metabolism*
  • Magnetic Fields
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Nanocomposites / chemistry*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • Osteogenesis / drug effects*
  • Signal Transduction
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Integrin alpha3
  • Magnetite Nanoparticles