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

Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany
Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany
Institut für Korrosionsschutz, Dresden GmbH, Gostritzer Straße 65, 01217 Dresden, Germany
Department of Dermatology and Allergology, Ludwig-Maximilians-University, Frauenlobstr. 9-11, 80337 Munich, Germany
Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, Goethestraße 70, 80336 Munich, Germany
Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany
Phylon Pharma Services, Newbury Park, CA 91320, USA
School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1002;
Received: 21 December 2018 / Revised: 1 February 2019 / Accepted: 21 February 2019 / Published: 26 February 2019
(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)
PDF [2595 KB, uploaded 26 February 2019]


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. View Full-Text
Keywords: nanofunctionalization; denosumab; osteoclast; titanium; implant nanofunctionalization; denosumab; osteoclast; titanium; implant

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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. Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes. Int. J. Mol. Sci. 2019, 20, 1002.

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