Cilostazol induces cellular senescence and confers resistance to etoposide-induced apoptosis in articular chondrocytes

Kim,Kang  Mi; Kim,Jong  Min; Yoo,Young  Hyun; Kim,Jeung  Il; Park,Young  Chul

doi:10.3892/ijmm.2012.892

Cilostazol induces cellular senescence and confers resistance to etoposide-induced apoptosis in articular chondrocytes

Authors:
- Kang Mi Kim
- Jong Min Kim
- Young Hyun Yoo
- Jeung Il Kim
- Young Chul Park
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Affiliations: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea, Department of Anatomy and Cell Biology, Dong-A University School of Medicine, Busan 602-714, Republic of Korea, Department of Orthopedic Surgery, Pusan National University Hospital, Busan 602-739, Republic of Korea
Published online on: January 23, 2012 https://doi.org/10.3892/ijmm.2012.892
Pages: 619-624

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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.

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