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

doi:10.3390/ijms20051002

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 language	English
Article number	1002
Number of pages	12
Journal	International journal of molecular sciences
Volume	20
Issue number	5
DOIs	https://doi.org/10.3390/ijms20051002
Publication status	Published - 1 Mar 2019
Externally published	Yes

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

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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. (2019). Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes. International journal of molecular sciences, 20(5), Article 1002. https://doi.org/10.3390/ijms20051002

@article{7be44a7525e947938d7a975fa56e20d5,

title = "Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes",

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 = "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",

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

note = "Funding Information: Funding: This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (MA 5158/1-1). The work of Felicitas Beck was supported by the “Promotionsstudium F{\"o}rderung f{\"u}r Forschung und Lehre” program from the University of Munich. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = mar,

day = "1",

doi = "10.3390/ijms20051002",

language = "English",

volume = "20",

journal = "International journal of molecular sciences",

issn = "1422-0067",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "5",

}

Beck, F, Hartmann, ES, Koehler, MI, Redeker, JI, Schluessel, S, Schmitt, B, Fottner, A, Unger, M, van Griensven, M, Michael, J, Summer, B, Kunzelmann, K-H, Beutner, R, Scharnweber, D, Kostenuik, PJ & Mayer-Wagner, S 2019, 'Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes', International journal of molecular sciences, vol. 20, no. 5, 1002. https://doi.org/10.3390/ijms20051002

TY - JOUR

T1 - Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes

AU - Beck, Felicitas

AU - Hartmann, Eliza S

AU - Koehler, Miriam I

AU - Redeker, Julia I

AU - Schluessel, Sabine

AU - Schmitt, Baerbel

AU - Fottner, Andreas

AU - Unger, Marina

AU - van Griensven, Martijn

AU - Michael, Jan

AU - Summer, Burkhard

AU - Kunzelmann, Karl-Heinz

AU - Beutner, Rene

AU - Scharnweber, Dieter

AU - Kostenuik, Paul J

AU - Mayer-Wagner, Susanne

N1 - Funding Information: Funding: This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (MA 5158/1-1). The work of Felicitas Beck was supported by the “Promotionsstudium Förderung für Forschung und Lehre” program from the University of Munich. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - Cell Differentiation/drug effects

KW - Denosumab/pharmacology

KW - Humans

KW - Macrophage Colony-Stimulating Factor/pharmacology

KW - Male

KW - Monocytes/cytology

KW - Nanoparticles/chemistry

KW - Osteogenesis/drug effects

KW - RANK Ligand/pharmacology

KW - Solubility

KW - Tartrate-Resistant Acid Phosphatase/metabolism

KW - Titanium/pharmacology

KW - RANKL

KW - titanium

KW - OPG

KW - IMPLANTS

KW - implant

KW - WEAR

KW - LIGAND

KW - denosumab

KW - RANKL/RANK/OPG SYSTEM

KW - MODEL

KW - ALENDRONATE

KW - PERIPROSTHETIC OSTEOLYSIS

KW - osteoclast

KW - nanofunctionalization

U2 - 10.3390/ijms20051002

DO - 10.3390/ijms20051002

M3 - Article

C2 - 30813507

SN - 1422-0067

VL - 20

JO - International journal of molecular sciences

JF - International journal of molecular sciences

IS - 5

M1 - 1002

ER -

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

Abstract

Keywords

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