title: Cilostazol induces cellular senescence and confers resistance to etoposide-induced             apoptosis in articular chondrocytes.
abstract: We recently reported that cilostazol protects chondrocytes against stress-induced             apoptosis and prevents cartilage destruction in an osteoarthritis (OA) model.             In the present study, we elucidate the mechanism underlying the protective effect             induced by cilostazol against stress-induced apoptosis in chondrocytes. Cilostazol             significantly reduced the expression of type II collagen and stimulated the accumulation             of β-catenin in primary rat articular chondrocytes. Moreover, cilostazol-induced             chondrocytes showed induction of senescent phenotypes, such as changes in cell             morphology, decrease in cell proliferation and increase in specific senescence-associated             β-galactosidase (SA-β-gal) staining. Moreover, dedifferentiated chondrocytes obtained             by serial subculture showed cellular senescence that increased with passage number.             In addition, the percentage of terminal dUTP nick end-labeling (TUNEL)-positive             cells was higher when chondrocytes were treated with cilostazol and the apoptosis             inducer etoposide than when the cells were treated with etoposide alone. Our findings             suggest that cilostazol induces dedifferentiation and senescence in rat articular             chondrocytes and renders them resistant to etoposide-induced apoptosis.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University                     School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Kang Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Jeung Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000077407:Cilostazol; D024043:Collagen Type II / Q000378:metabolism; D005047:Etoposide / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013777:Tetrazoles / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D013777:Tetrazoles; D051176:beta Catenin; D005047:Etoposide; D001616:beta-Galactosidase; D000077407:Cilostazol