Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence

Kim,Kang  Mi; Park,Si  Eun; Lee,Mi  Sun; Kim,Koanhoi; Park,Young  Chul

doi:10.3892/ijmm.2014.1918

Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence

Authors:
- Kang Mi Kim
- Si Eun Park
- Mi Sun Lee
- Koanhoi 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 Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongnam 626‑870, Republic of Korea, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Gyeongnam 626‑870, Republic of Korea
Published online on: August 29, 2014 https://doi.org/10.3892/ijmm.2014.1918
Pages: 1335-1340

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Abstract

Chondrocyte senescence is associated with the aging and degeneration of cartilage, and eventually leads to joint destruction. The aim of this study was to elucidate the mechanisms responsible for the cytoprotective effects of heme oxygenase‑1 (HO‑1) on chondrocytes in cartilage. Chondrocyte senescence was induced using cilostazol and measured using a specific senescence‑associated β‑galactosidase (SA‑β‑gal) staining assay. Cilostazol altered the expression of type Ⅱ collagen and β‑catenin, which are phenotypic markers of the differentiation and dedifferentiation of chondrocytes. Cilostazol also significantly induced HO‑1 expression, and the induction of HO‑1 expression was affected by a significant increase in reactive oxygen species (ROS) production caused by cilostazol treatment. Of note, pre‑treatment with 3‑morpholinosydnonimine hydrochloride (SIN‑1), an inducer of HO‑1 expression, markedly attenuated cilostazol‑induced chondrocyte senescence, and thus, we examined whether HO‑1 directly modulates chondrocyte senescence induced by cilostazol. The upregulation of HO‑1 was found to suppress cilostazol‑induced cellular senescence. In addition, the inhibition of HO‑1 activity with the iron chelator, desferrioxamine (DFO), or HO‑1 siRNA increased cilostazol‑induced chondrocyte senescence. Based on these results, it can be concluded that HO‑1 is associated with the suppression of chondrocyte senescence, and that the enforced overexpression of HO‑1 protects chondrocytes against stress‑induced senescence.

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