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

Journal: International journal of molecular sciences 2019;20(5):1002

PMID: 30813507

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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.

Address: Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].; Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. [email protected].; Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. [email protected].; Institut für Korrosionsschutz, Dresden GmbH, Gostritzer Straße 65, 01217 Dresden, Germany. [email protected].; Department of Dermatology and Allergology, Ludwig-Maximilians-University, Frauenlobstr. 9-11, 80337 Munich, Germany. [email protected].; Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, Goethestraße 70, 80336 Munich, Germany. [email protected].; Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany. [email protected].; Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany. [email protected].; Phylon Pharma Services, Newbury Park, CA 91320, USA. [email protected].; School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].; Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany. [email protected].

DOI: 10.3390/ijms20051002

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MeSH Terms: Cell Differentiation, Denosumab, Humans, Macrophage Colony-Stimulating Factor, Male, Monocytes, Nanoparticles, Osteogenesis, RANK Ligand, Solubility, Tartrate-Resistant Acid Phosphatase, Titanium