ArticleClinical oral investigations2015
Zoledronate but not denosumab suppresses macrophagic differentiation of THP-1 cells. An aetiologic model of bisphosphonate-related osteonecrosis of the jaw (BRONJ).
Article in Clinical oral investigations, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- New Immunological Insights into Bisphosphonate-Related Osteonecrosis of the Jaw: A Multidimensional Reappraisal from Molecular Switches to Clinical Phenotypes.Current issues in molecular biology · 2026Review
- [Expert consensus on perioperative management of tooth extraction in patients receiving denosumab therapy].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Article
- Etiopathogenesis of medication-related osteonecrosis of the jaws: a review.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Article
- Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw.International journal of molecular sciences · 2023Review
- [Latest Research Findings on Immune Microenvironment Regulation in Jawbone-Related Diseases].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- Macrophage Involvement in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Comprehensive, Short Review.Cancers · 2022Review
- Quantitative evaluation of Mycobacterium abscessus clinical isolate virulence using a silkworm infection model.PloS one · 2022Article
- The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw.Frontiers in immunology · 2021Review
- Extensive protein expression changes induced by pamidronate in RAW 264.7 cells as determined by IP-HPLC.PeerJ · 2020Article
- Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials.The Journal of international medical research · 2018Review
- Macrophages and skeletal health.Pharmacology & therapeutics · 2017Review
- Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw.The Journal of biological chemistry · 2016Article
- Altered macrophagic THP-1 cell phagocytosis and migration in bisphosphonate-related osteonecrosis of the jaw (BRONJ).Clinical oral investigations · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesBisphosphonates and denosumab are antiresorptive drugs used for the treatment of osteoporosis and oncological tumors. A severe side effect is osteonecrosis of the jaw. Monocyte/macrophage dysfunction is considered to play a distinct role in osteonecrosis. THP-1 monocytic cells were used in this study to elucidate the influence of zoledronate and denosumab on phorbol-12-myrisate-13-acetate (PMA)-induced macrophage differentiation and function in real-time. MATERIALS AND
methodsMacrophagic differentiation of the THP-1 suspension cells was measured by cell adherence in the presence or absence of different concentrations of zoledronate (0.5, 5, 50 μM) and denosumab (1, 10, 20, 40 μg/mL) using the real-time xCELLigence system. Additionally, a live/dead staining was performed by fluorescence microscopy.
resultsTHP-1 cells demonstrated a regular initial PMA-induced differentiation to macrophages by live measurements of cell adherence and by an increase in CD68 surface expression as detected by flow cytometry. The addition of zoledronate led to cell detachment of the THP-1-derived macrophages in a dose-dependent manner in contrast to denosumab. Cell detachment was based on cell death as confirmed by live/dead staining, revealing elevated numbers of dead cells following addition of high zoledronate concentrations. However, denosumab did not deteriorate THP-1 cell viability.
conclusionOur results demonstrate that zoledronate but not denosumab suppresses monocytic THP-1 cell viability after macrophagic differentiation dose-dependently. CLINICAL RELEVANCE: This is the first real-time study providing evidence for a dose-dependent immunosuppressive effect of zoledronate in contrast to denosumab on local macrophages.
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