Strontium-loaded titania nanotube arrays repress osteoclast differentiation through multiple signalling pathways: In vitro and in vivo studies

Sci Rep. 2017 May 24;7(1):2328. doi: 10.1038/s41598-017-02491-9.

Abstract

The loosening of implants is an important clinical issue, particularly for patients with osteoporosis. In these patients, an implant should preferably both promote osteoblast differentiation and repress osteoclastic resorption. In the present study, we fabricated coatings containing TiO2 nanotubes (NTs) incorporated with strontium (Sr) on titanium (Ti) surfaces through hydrothermal treatment. The amount of loaded Sr was controlled by hydrothermally treating the samples in a Sr(OH)2 solution for 1 and 3 h (samples NT-Sr1h and NT-Sr3h, respectively) and found that both types of NT-Sr samples inhibited osteoclast differentiation by reducing the expression of osteoclast marker genes. Additionally, this inhibitory effect was mainly attributed to suppression of RANKL-induced activation of nuclear factor-κB (NF-κB). Moreover, NT-Sr also inhibited the Akt and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) signalling pathways. Interestingly, we also found that NT-Sr promoted RANKL-induced extracellular signal-regulated kinase (ERK) phosphorylation. Using ovariectomised rats as a model, we observed that NT-Sr prevented bone loss in vivo. In conclusion, our findings demonstrate that NT-Sr might effectively inhibit osteoclast differentiation by repressing the NF-κB and Akt/NFATc1 pathways and by negatively regulating the ERK pathway in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / genetics
  • Bone Resorption / physiopathology
  • Bone Resorption / prevention & control*
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mice
  • NFATC Transcription Factors / genetics
  • Nanotubes / chemistry*
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects*
  • Osteoporosis / genetics
  • Osteoporosis / physiopathology
  • Osteoporosis / prevention & control*
  • Osteoporosis / surgery
  • RANK Ligand / genetics
  • Rats
  • Strontium / chemistry
  • Strontium / therapeutic use
  • Titanium / chemistry
  • Titanium / therapeutic use

Substances

  • NFATC Transcription Factors
  • RANK Ligand
  • titanium dioxide
  • Titanium
  • Strontium