Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Cell Cultures
2.3. Analysis of sRANKL-Activated Neddylation Pathway
2.4. Cell Viability Assay
2.5. UBA3 Knockdown
2.6. Osteoclast Differentiation Assay
2.7. Cathepsin K Activity and Pit Assays
2.8. Analysis of sRANKL-Activated Downstream Signaling
2.9. Immunoprecipitation and Western Blotting
2.10. sRANKL Combined Ovariectomy-Induced Osteoporosis Mouse Model
2.11. Micro-CT Scanning
2.12. Biomechanical Testing
2.13. Histological Analysis
2.14. Osteogenic Differentiation and Alizarin Red S Stain
2.15. Statistical Analyses
3. Results
3.1. Neddylation Pathway Is Upregulated in sRANKL-Mediated Osteoclastogenesis
3.2. UBA3 Knockdown Attenuates Osteoclast Differentiation in RAW 264.7 Cells
3.3. Inhibition of Neddylation Significantly Suppresses Osteoclast Differentiation in sRANKL-Stimulated Macrophages
3.4. Inhibition of Neddylation by MLN4924 Diminishes sRANKL-Activated Downstream Signaling
3.5. Assessment of MLN4924 Treatment on OVX/sRANKL-Mediated Bone Loss In Vivo and Biomechanical Properties
3.6. Effect of MLN4924 on Osteoblast Differentiation in MC3T3-E1 Cells
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wu, M.-H.; Hsu, W.-B.; Chen, M.-H.; Shi, C.-S. Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo. Biomedicines 2022, 10, 2355. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102355
Wu M-H, Hsu W-B, Chen M-H, Shi C-S. Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo. Biomedicines. 2022; 10(10):2355. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102355
Chicago/Turabian StyleWu, Meng-Huang, Wei-Bin Hsu, Mei-Hsin Chen, and Chung-Sheng Shi. 2022. "Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo" Biomedicines 10, no. 10: 2355. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102355