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

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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.

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          Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab.

          David L. Lacey, William J. Boyle, W. Simonet … (2012)
          Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.
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            Aseptic loosening, not only a question of wear: a review of different theories.

            Christina Gretzer, Mikael Sundfeldt, L. Carlsson … (2006)
            Today, aseptic loosening is the most common cause of revision of major arthroplasties. Aseptic loosening accounts for more than two-thirds of hip revisions and almost one-half of knee revisions in Sweden. Several theories on the cause of aseptic loosening have been proposed. Most of these theories, however, are based on empiric observations, experimental animal models or anecdotal cases. In this review, we discuss the most common theories concerning aseptic loosening. It emerges from this review that aseptic loosening has a multifactorial etiology and cannot be explained by a single theory.
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              Bioactive Coatings for Orthopaedic Implants—Recent Trends in Development of Implant Coatings

              Bill Zhang, Damian Myers, Gordon G. Wallace … (2014)
              Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 26 February 2019
                Publication date Collection: March 2019
                Volume: 20
                Issue: 5
                Electronic Location Identifier: 1002
                Affiliations
                [1 ]Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany; Huber.felicitas@ 123456googlemail.com (F.B.); elizahartmann@ 123456msn.com (E.S.H.); miriam.koehler@ 123456gwweb.de (M.I.K.); julia.redeker@ 123456icloud.com (J.I.R.); Sabine.Schluessel@ 123456med.uni-muenchen.de (S.S.); baerbel.schmitt@ 123456med.uni-muenchen.de (B.S.); andreas.fottner@ 123456med.uni-muenchen.de (A.F.)
                [2 ]Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany; unger@ 123456uchir.me.tum.de (M.U.); martijn.vangriensven@ 123456tum.de (M.v.G.)
                [3 ]Institut für Korrosionsschutz, Dresden GmbH, Gostritzer Straße 65, 01217 Dresden, Germany; jannaj@ 123456gmx.de
                [4 ]Department of Dermatology and Allergology, Ludwig-Maximilians-University, Frauenlobstr. 9-11, 80337 Munich, Germany; burkhard.summer@ 123456med.uni-muenchen.de
                [5 ]Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, Goethestraße 70, 80336 Munich, Germany; Karl-Heinz.Kunzelmann@ 123456med.uni-muenchen.de
                [6 ]Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany; rene.beutner@ 123456tu-dresden.de (R.B.); dieter.scharnweber@ 123456tu-dresden.de (D.S.)
                [7 ]Phylon Pharma Services, Newbury Park, CA 91320, USA; PKost@ 123456PhylonPS.com
                [8 ]School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-5104-9881
                https://orcid.org/0000-0003-0369-5189
                https://orcid.org/0000-0001-6391-4086
                Article
                Publisher ID: ijms-20-01002
                DOI: 10.3390/ijms20051002
                PMC ID: 6429431
                PubMed ID: 30813507
                SO-VID: e10d4d48-962b-4586-9a8d-1faec1838160
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 21 December 2018
                Date accepted : 21 February 2019
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: nanofunctionalization,denosumab,osteoclast,titanium,implant
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: nanofunctionalization, denosumab, osteoclast, titanium, implant

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