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Alpha B-Crystallin Protects Rat Articular Chondrocytes against Casein Kinase II Inhibition-Induced Apoptosis.
- Source :
-
PloS one [PLoS One] 2016 Nov 16; Vol. 11 (11), pp. e0166450. Date of Electronic Publication: 2016 Nov 16 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Although alpha (α)B-crystallin is expressed in articular chondrocytes, little is known about its role in these cells. Protein kinase casein kinase 2 (CK2) inhibition induces articular chondrocyte death. The present study examines whether αB-crystallin exerts anti-apoptotic activity in articular chondrocytes. Primary rat articular chondrocytes were isolated from knee joint slices. Cells were treated with CK2 inhibitors with or without αB-crystallin siRNA. To examine whether the silencing of αB-crystallin sensitizes rat articular chondrocytes to CK2 inhibition-induced apoptosis, we assessed apoptosis by performing viability assays, mitochondrial membrane potential measurements, flow cytometry, nuclear morphology observations, and western blot analysis. To investigate the mechanism by which αB-crystallin modulates the extent of CK2 inhibition-mediated chondrocyte death, we utilized confocal microscopy to observe the subcellular location of αB-crystallin and its phosphorylated forms and performed a co-immunoprecipitation assay to observe the interaction between αB-crystallin and CK2. Immunochemistry was employed to examine αB-crystallin expression in cartilage obtained from rats with experimentally induced osteoarthritis (OA). Our results demonstrated that silencing of αB-crystallin sensitized rat articular chondrocytes to CK2 inhibitor-induced apoptosis. Furthermore, CK2 inhibition modulated the expression and subcellular localization of αB-crystallin and its phosphorylated forms and dissociated αB-crystallin from CK2. The population of rat articular chondrocytes expressing αB-crystallin and its phosphorylated forms was reduced in an experimentally induced rat model of OA. In summary, αB-crystallin protects rat articular chondrocytes against CK2 inhibition-induced apoptosis. αB-crystallin may represent a suitable target for pharmacological interventions to prevent OA.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Apigenin pharmacology
Benzimidazoles pharmacology
Casein Kinase II metabolism
Chondrocytes drug effects
Chondrocytes metabolism
Disease Models, Animal
Gene Knockdown Techniques
Gene Silencing drug effects
Male
Osteoarthritis chemically induced
Osteoarthritis metabolism
Osteoarthritis pathology
Phenotype
Phosphorylation drug effects
Protein Transport drug effects
Rats, Sprague-Dawley
Subcellular Fractions drug effects
Subcellular Fractions metabolism
Triazoles pharmacology
Apoptosis drug effects
Cartilage, Articular cytology
Casein Kinase II antagonists & inhibitors
Chondrocytes cytology
Cytoprotection drug effects
alpha-Crystallin B Chain metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27851782
- Full Text :
- https://doi.org/10.1371/journal.pone.0166450