Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage
Abstract
:1. Introduction
2. Results
2.1. Tigecycline and Minocycline Suppress MMP-9-Mediated H3 Tail Cleavage
2.2. Tigecycline and Minocycline Inhibit Osteoclastogenesis by Negatively Regulating Osteoclast-Specific Genes
2.3. Tigecycline and Minocycline Do Not Affect Osteoblast Differentiation
2.4. Tigecycline and Minocycline Suppress Prednisolone-Induced Osteoporosis in Zebrafish Larvae
3. Discussion
4. Materials and Methods
4.1. Plasmid Construction and Materials
4.2. Docking Simulation of MMP-9 with Tetracyclines
4.3. Osteoclast Differentiation and H3NT Cleavage Analysis
4.4. In Vitro H3NT Cleavage Assays
4.5. Osteoblast Differentiation and Alizarin Red S Staining
4.6. RT-qPCR
4.7. Cell Proliferation Assay
4.8. Fish Maintenance and Drug Treatment
4.9. Whole-Mount Skeletal Staining
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
RANK | Receptor activator of nuclear factor kappaB |
RANKL | Receptor activator of the NF-κB ligand |
MMP | Matrix metalloproteinase |
BMM | Bone marrow-derived macrophage |
GIO | Glucocorticoid-induced osteoporosis |
TRAP | Tartrate-resistant acid phosphatase |
ALP | Alkaline phosphatase |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide |
Runx2 | Runt-related transcription factor 2 |
ALP | Alkaline phosphatase |
BSP | Bone sialoprotein |
HEPES | 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid |
DTT | Dithiothreitol |
EDTA | Ethylenediaminetetraacetic acid |
EGTA | Ethylene glycol tetraacetic acid |
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Kim, Y.; Kim, J.; Lee, H.; Shin, W.-R.; Lee, S.; Lee, J.; Park, J.-I.; Jhun, B.H.; Kim, Y.-H.; Yi, S.-J.; et al. Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage. Int. J. Mol. Sci. 2019, 20, 4038. https://doi.org/10.3390/ijms20164038
Kim Y, Kim J, Lee H, Shin W-R, Lee S, Lee J, Park J-I, Jhun BH, Kim Y-H, Yi S-J, et al. Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage. International Journal of Molecular Sciences. 2019; 20(16):4038. https://doi.org/10.3390/ijms20164038
Chicago/Turabian StyleKim, Yeojin, Jinman Kim, Hyerim Lee, Woo-Ri Shin, Sheunghun Lee, Jisu Lee, Jae-Il Park, Byung Hak Jhun, Yang-Hoon Kim, Sun-Ju Yi, and et al. 2019. "Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage" International Journal of Molecular Sciences 20, no. 16: 4038. https://doi.org/10.3390/ijms20164038