title: Alpha B-Crystallin Protects Rat Articular Chondrocytes against Casein Kinase II Inhibition-Induced Apoptosis.
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.
authors.affiliation: Department of Rheumatology, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Sung Won
authors.identifier: http://orcid.org/0000-0003-1213-1254
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Rho
authors.affiliation: Department of Rheumatology, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Sang Yeob
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Chung
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
chemical_list: C405354:4,5,6,7-tetrabromobenzotriazole; C110962:5,6-dichlorobenzimidazole; D001562:Benzimidazoles; D014230:Triazoles; D038203:alpha-Crystallin B Chain; D047310:Apigenin; D047390:Casein Kinase II