Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes

Int J Mol Sci. 2019 Feb 26;20(5):1002. doi: 10.3390/ijms20051002.

Abstract

Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces.

Keywords: denosumab; implant; nanofunctionalization; osteoclast; titanium.

MeSH terms

  • Cell Differentiation / drug effects
  • Denosumab / pharmacology*
  • Humans
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Male
  • Monocytes / cytology*
  • Monocytes / drug effects*
  • Monocytes / ultrastructure
  • Nanoparticles / chemistry
  • Osteogenesis / drug effects*
  • RANK Ligand / pharmacology
  • Solubility
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Titanium / pharmacology*

Substances

  • RANK Ligand
  • Denosumab
  • Macrophage Colony-Stimulating Factor
  • Titanium
  • Tartrate-Resistant Acid Phosphatase