Mosch, Alexander and Ettl, Tobias and Mamilos, Andreas and Schreml, Stephan and Spoerl, Steffen and Spanier, Gerrit and Klingelhoeffer, Christoph (2019) Physiological concentrations of denosumab enhance osteogenic differentiation in human mesenchymal stem cells of the jaw bone. ARCHIVES OF ORAL BIOLOGY, 101. pp. 23-29. ISSN 0003-9969, 1879-1506
Full text not available from this repository. (Request a copy)Abstract
Objective: The aim of this study was to evaluate the possible influence of denosumab and zoledronate on pro-liferation and osteogenic differentiation of alveolar bone stem cells. Design: Mesenchymal stem cells (MSCs) and dental follicle cells (DFCs) were grown under osteogenic differentiation with concentrations from 0.25 mu M to 10 mu M (zoledronate) and to 20 mu M (denosumab). Vitality was assessed after 7 days by CCK-8 Kit. Osteogenic differentiation was measured by alkaline phosphatase (ALP) assay and additionally by RT-qPCR of key enzymes COL1, RUNX2 and ALP. Results: MSCs expressed receptor activator of NF-kappa B (RANK), as requirement to interact with denosumab. DFCs did not express RANK. Denosumab significantly reduced proliferation and ALP activity of MSCs in high concentrations (10 mu M and 20 mu M). Growth of DFCs was not influenced at all by denosumab. Zoledronate reduced proliferation of DFCs in higher concentrations (5 mu M and 10 mu M) (p > 0.05). Physiological and medium concentrations of denosumab (0.25 mu M, 1 mu M 5 mu M) significantly enhanced ALP activity in MSCs and COL1, RUNX2 and ALP were upregulated. Zoledronate had no effect on ALP activity in DFCs. Conclusion: Our evaluations suggest receptor and dose depending effects of denosumab in MSCs. High concentrations mediate toxic effects, whereas physiological and medium concentrations enhance osteogenic differentiation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ZOLEDRONIC ACID; MEVALONATE PATHWAY; GENE-EXPRESSION; BISPHOSPHONATES; GERANYLGERANIOL; OSTEONECROSIS; DEXAMETHASONE; CULTURE; WOMEN; Denosumab; Medication-related osteonecrosis of the jaw; Osteogenic differentiation; Zoledronate; Mesenchymal stem cells; Dental follicle cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2020 07:10 |
| Last Modified: | 09 Apr 2020 07:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27091 |
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