Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes

Kim,Kang Mi; Sohn,Dong Hyun; Kim,Koanhoi; Park,Young Chul

doi:10.3892/ijmm.2018.4016

Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes

Authors:
- Kang Mi Kim
- Dong Hyun Sohn
- Koanhoi Kim
- Young Chul Park
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Affiliations: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea, Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea
Published online on: December 4, 2018 https://doi.org/10.3892/ijmm.2018.4016
Pages: 1033-1040

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Abstract

Protein kinase casein kinase 2 (CK2) is important in the regulation of cell proliferation and death, even under pathological conditions. Previously, we reported that CK2 regulates the expression of heme oxygenase‑1 (HO‑1) in stress‑induced chondrocytes. In the present study, it was shown that CK2 is involved in the dedifferentiation and cellular senescence of chondrocytes. Treatment of primary articular chondrocytes with CK2 inhibitors, 4,5,6,7‑terabromo‑2‑azabenzimidazole (TBB) or 5,6‑dichlorobenzimidazole 1‑β‑D‑ribofuranoside (DRB), induced an increase in senescence‑associated β‑galactosidase (SA‑β‑gal) staining. In addition, TBB reduced the expression of type II collagen and stimulated the accumulation of β‑catenin, phenotypic markers of chondrocyte differentiation and dedifferentiation, respectively. It was also observed that the abrogation of CK2 activity by CK2 small interfering RNA induced phenotypes of chondrocyte senescence. The association between HO‑1 and cellular senescence was also examined in CK2 inhibitor‑treated chondrocytes. Pretreatment with 3‑morpholinosydnonimine hydrochloride, an inducer of the HO‑1 expression, or overexpression of the HO‑1 gene significantly delayed chondrocyte senescence. These results show that CK2 is associated with chondrocyte differentiation and cellular senescence and that this is due to regulation of the expression of HO‑1. Furthermore, the findings suggest that CK2 is crucial as an anti‑aging factor during chondrocyte senescence.

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