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Aquaporin-4 Blockage by siRNA Protects Rat Articular Chondrocytes from IL-1β-induced Apoptosis by Inhibiting p38 MAPK Signal Pathway.
- Source :
-
Annals of clinical and laboratory science [Ann Clin Lab Sci] 2017 Sep; Vol. 47 (5), pp. 563-571. - Publication Year :
- 2017
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Abstract
- Accumulating evidence reveals that articular chondrocytes undergo increased apoptosis in rheumatoid arthritis (RA) and inhibiting chondrocyte apoptosis might be a promising therapeutic strategy. We recently found that aquaporin-4 (AQP4) protein level in the cartilage of rats with adjuvant-induced arthritis was higher than normal rats. Herein, cultured rat articular chondrocyte impaired by interleukin-1 beta (IL-1β) was used as an in vitro model of chondrocyte apoptosis. We observed the protective effect of AQP4 blockage by siRNA on IL-1β-induced chondrocyte apoptosis and explored the underlying mechanisms. Our findings revealed that AQP4 siRNA protected articular chondrocytes from IL-1β-induced apoptosis, evidenced by increased cell proliferation (MTT assay), few observations of apoptotic morphologic changes (Hoechst 33258 staining assay) and decreased cell apoptosis rates (Annexin V-FITC/PI staining assay). Additionally, AQP4 siRNA remarkably decreased Bax and caspase 3 mRNA levels and increased Bcl-2 mRNA level, accompanied by reducing phosphorylated-p38 (P-p38) protein level, without affecting p38 protein. The above effects of AQP4 siRNA were similar to SB203580, a specific p38 inhibitor. Together, AQP4 siRNA attenuated IL-1β-induced chondrocyte apoptosis by regulating apoptosis-related gene expressions and inhibiting p38 MAPK. Our results provide experimental evidence that AQP4 inhibition contributes to preventing chondrocyte apoptosis in joint diseases such as RA and provide a novel therapeutic target for RA.<br /> (© 2017 by the Association of Clinical Scientists, Inc.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Apoptosis Regulatory Proteins agonists
Apoptosis Regulatory Proteins antagonists & inhibitors
Apoptosis Regulatory Proteins genetics
Apoptosis Regulatory Proteins metabolism
Aquaporin 4 genetics
Aquaporin 4 metabolism
Cartilage, Articular cytology
Cartilage, Articular drug effects
Cartilage, Articular immunology
Cell Proliferation drug effects
Cells, Cultured
Chondrocytes cytology
Chondrocytes drug effects
Chondrocytes immunology
Enzyme Activation drug effects
Gene Expression Regulation drug effects
Imidazoles pharmacology
Interleukin-1beta genetics
Phosphorylation drug effects
Protein Kinase Inhibitors pharmacology
Protein Processing, Post-Translational drug effects
Pyridines pharmacology
RNA Interference
Rats, Sprague-Dawley
Recombinant Proteins metabolism
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases metabolism
Apoptosis drug effects
Aquaporin 4 antagonists & inhibitors
Cartilage, Articular metabolism
Chondrocytes metabolism
Down-Regulation drug effects
Interleukin-1beta metabolism
MAP Kinase Signaling System drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1550-8080
- Volume :
- 47
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Annals of clinical and laboratory science
- Publication Type :
- Academic Journal
- Accession number :
- 29066483