A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts
Abstract
:1. Introduction
2. Materials and Methods
2.1. Antibodies
2.2. Cell Culture
2.3. Cyclic Biaxial Tensile Strain
2.4. RNAi Silencing in SF
2.5. ArrayStar LncRNA Array
2.6. Inhibitor Assays
2.7. Semi-Quantitative qPCR
2.8. NAD+ Assays
2.9. Reactive Oxygen Species (ROS) Assays
2.10. ATP Assays
2.11. Preparation of Cell Lysates and Western Blotting
2.12. Preparation of Nuclear Fractions
2.13. Co-Immunoprecipitation
2.14. Enrichment of Plasma Membrane by Cell Surface Biotinylation
2.15. Immunofluorescence
2.16. Statistical Analysis
3. Results
3.1. Downregulation of lncRNA HOTAIR by Mechanical Strain Is Critically Dependent on ADAM15
3.2. Strain-Induced SIRT1 Upregulation via ADAM15-Mediated Downregulation of HOTAIR
3.3. Impact of ADAM15 and SIRT1 on Histone Acetylation, ROS and NAD+
3.4. Impact of JNK on ADAM15-Dependent Mechano-Signaling in HOTAIR/SIRT1 Regulation
3.5. Mechano-Induced Activation of TRPV4 and CAMK Upstream of JNK
3.6. Impact of ADAM15 and Calcium Signaling on Strain-Induced ATP Release
3.7. PANX1 Activity Is Controlled by ADAM15
3.8. Binding of ADAM15 to TRPV4 Is Critical for Its Membrane Localization
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
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Janczi, T.; Meier, F.; Fehrl, Y.; Kinne, R.W.; Böhm, B.; Burkhardt, H. A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts. Cells 2021, 10, 2705. https://doi.org/10.3390/cells10102705
Janczi T, Meier F, Fehrl Y, Kinne RW, Böhm B, Burkhardt H. A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts. Cells. 2021; 10(10):2705. https://doi.org/10.3390/cells10102705
Chicago/Turabian StyleJanczi, Tomasz, Florian Meier, Yuliya Fehrl, Raimund W. Kinne, Beate Böhm, and Harald Burkhardt. 2021. "A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts" Cells 10, no. 10: 2705. https://doi.org/10.3390/cells10102705