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

Felicitas Beck, Eliza S Hartmann, Miriam I Koehler, Julia I Redeker, Sabine Schluessel, Baerbel Schmitt, Andreas Fottner, Marina Unger, Martijn van Griensven, Jan Michael, Burkhard Summer, Karl-Heinz Kunzelmann, Rene Beutner, Dieter Scharnweber, Paul J Kostenuik, Susanne Mayer-Wagner

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number1002
Number of pages12
JournalInternational journal of molecular sciences
Volume20
Issue number5
DOIs
Publication statusPublished - 1 Mar 2019
Externally publishedYes

Keywords

  • Cell Differentiation/drug effects
  • Denosumab/pharmacology
  • Humans
  • Macrophage Colony-Stimulating Factor/pharmacology
  • Male
  • Monocytes/cytology
  • Nanoparticles/chemistry
  • Osteogenesis/drug effects
  • RANK Ligand/pharmacology
  • Solubility
  • Tartrate-Resistant Acid Phosphatase/metabolism
  • Titanium/pharmacology
  • RANKL
  • titanium
  • OPG
  • IMPLANTS
  • implant
  • WEAR
  • LIGAND
  • denosumab
  • RANKL/RANK/OPG SYSTEM
  • MODEL
  • ALENDRONATE
  • PERIPROSTHETIC OSTEOLYSIS
  • osteoclast
  • nanofunctionalization

Cite this

Beck, F., Hartmann, E. S., Koehler, M. I., Redeker, J. I., Schluessel, S., Schmitt, B., Fottner, A., Unger, M., van Griensven, M., Michael, J., Summer, B., Kunzelmann, K-H., Beutner, R., Scharnweber, D., Kostenuik, P. J., & Mayer-Wagner, S. (2019). Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes. International journal of molecular sciences, 20(5), [1002]. https://doi.org/10.3390/ijms20051002