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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 1033-1040
    |
    Published online on: December 4, 2018
       https://doi.org/10.3892/ijmm.2018.4016
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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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1 

Sandell LJ and Adler P: Developmental patterns of cartilage. Front Biosci. 4:D731–D742. 1999. View Article : Google Scholar

2 

DeLise AM, Fischer L and Tuan RS: Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage. 8:309–334. 2000. View Article : Google Scholar

3 

Goldring MB: The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 43:1916–1926. 2000. View Article : Google Scholar

4 

Roughley PJ: Articular cartilage and changes in arthritis: Noncollagenous proteins and proteoglycans in the extracellular matrix of cartilage. Arthritis Res. 3:342–347. 2001. View Article : Google Scholar

5 

Guillén M, Megías J, Gomar F and Alcaraz M: Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes. J Pathol. 214:515–522. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Cawston T, Billington C, Cleaver C, Elliott S, Hui W, Koshy P, Shingleton B and Rowan A: The regulation of MMPs and TIMPs in cartilage turnover. Ann N Y Acad Sci. 878:120–129. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Kim HA and Song YW: Apoptotic chondrocyte death in rheumatoid arthritis. Arthritis Rheum. 42:1528–1537. 1999. View Article : Google Scholar

8 

Aigner T and Kim HA: Apoptosis and cellular vitality: Issues in osteoarthritic cartilage degeneration. Arthritis Rheum. 46:1986–1996. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Jallali N, Ridha H, Thrasivoulou C, Underwood C, Butler PE and Cowen T: Vulnerability to ROS-induced cell death in ageing articular cartilage: The role of antioxidant enzyme activity. Osteoarthritis Cartilage. 13:614–622. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Zwerina J, Tzima S, Hayer S, Redlich K, Hoffmann O, Hanslik-Schnabel B, Smolen JS, Kollias G and Schett G: Heme oxygenase 1 (HO-1) regulates osteoclastogenesis and bone resorption. FASEB J. 19:2011–2013. 2005. View Article : Google Scholar

11 

Loeser RF: Aging and osteoarthritis: The role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage. 17:971–979. 2009. View Article : Google Scholar :

12 

Martin JA and Buckwalter JA: Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology. 3:257–264. 2002. View Article : Google Scholar

13 

McCulloch K, Litherland GJ and Rai TS: Cellular senescence in osteoarthritis pathology. Aging Cell. 16:210–218. 2017. View Article : Google Scholar

14 

Litchfield DW: Protein kinase CK2: Structure, regulation and role in cellular decisions of life and death. Biochem J. 369:1–15. 2003. View Article : Google Scholar

15 

Meggio F and Pinna LA: One-thousand-and-one substrates of protein kinase CK2. FASEB J. 17:349–368. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Pinna LA: Casein kinase 2: An ’eminence grise’ in cellular regulation? Biochim Biophys Acta. 1054:267–284. 1990. View Article : Google Scholar

17 

Ahmed K, Gerber DA and Cochet C: Joining the cell survival squad: An emerging role for protein kinase CK2. Trends Cell Biol. 12:226–230. 2002. View Article : Google Scholar

18 

Faust RA, Gapany M, Tristani P, Davis A, Adams GL and Ahmed K: Elevated protein kinase CK2 activity in chromatin of head and neck tumors: Association with malignant transformation. Cancer Lett. 101:31–35. 1996. View Article : Google Scholar

19 

Ahmad KA, Wang G, Unger G, Slaton J and Ahmed K: Protein kinase CK2 - a key suppressor of apoptosis. Adv Enzyme Regul. 48:179–187. 2008. View Article : Google Scholar

20 

Drygin D, Ho CB, Omori M, Bliesath J, Proffitt C, Rice R, Siddiqui-Jain A, O’Brien S, Padgett C, Lim JK, et al: Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer. Biochem Biophys Res Commun. 415:163–167. 2011. View Article : Google Scholar

21 

Yoon YM, Kim SJ, Oh CD, Ju JW, Song WK, Yoo YJ, Huh TL and Chun JS: Maintenance of differentiated phenotype of articular chondrocytes by protein kinase C and extracellular signal-regulated protein kinase. J Biol Chem. 277:8412–8420. 2002. View Article : Google Scholar

22 

Lee SW, Song YS, Lee SY, Yoon YG, Lee SH, Park BS, Yun I, Choi H, Kim K, Chung WT, et al: Downregulation of protein kinase CK2 activity facilitates tumor necrosis factor-α-mediated chondrocyte death through apoptosis and autophagy. PLoS One. 6:e191632011. View Article : Google Scholar

23 

Kim KM, Song JD, Chung HT and Park YC: Protein kinase CK2 mediates peroxynitrite-induced heme oxygenase-1 expression in articular chondrocytes. Int J Mol Med. 29:1039–1044. 2012.PubMed/NCBI

24 

Kim KM, Park SE, Lee MS, Kim K and Park YC: Induction of heme oxygenase-1 expression protects articular chondrocytes against cilostazol-induced cellular senescence. Int J Mol Med. 34:1335–1340. 2014. View Article : Google Scholar

25 

Muir H: The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules. BioEssays. 17:1039–1048. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E and Aigner T: Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum. 46:2648–2657. 2002. View Article : Google Scholar

27 

Henrotin YE, Bruckner P and Pujol JP: The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis Cartilage. 11:747–755. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Phillips DC, Dias HK, Kitas GD and Griffiths HR: Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): Causes and consequences for immune function, cell survival, and therapeutic intervention. Antioxid Redox Signal. 12:743–785. 2010. View Article : Google Scholar

29 

Martin WJ, Herst PM, Chia EW and Harper JL: Sesquiterpene dialdehydes inhibit MSU crystal-induced superoxide production by infiltrating neutrophils in an in vivo model of gouty inflammation. Free Radic Biol Med. 47:616–621. 2009. View Article : Google Scholar

30 

Deahl ST II, Oberley LW, Oberley TD and Elwell JH: Immunohistochemical identification of superoxide dismutases, catalase, and glutathione-S-transferases in rat femora. J Bone Miner Res. 7:187–198. 1992. View Article : Google Scholar

31 

Borsiczky B, Szabó Z, Jaberansari MT, Mack PP and Röth E: Activated PMNs lead to oxidative stress on chondrocytes: A study of swine knees. Acta Orthop Scand. 74:190–195. 2003. View Article : Google Scholar

32 

Matés JM, Pérez-Gómez C and Núñez de Castro I: Antioxidant enzymes and human diseases. Clin Biochem. 32:595–603. 1999. View Article : Google Scholar

33 

Stadler J, Stefanovic-Racic M, Billiar TR, Curran RD, McIntyre LA, Georgescu HI, Simmons RL and Evans CH: Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol. 147:3915–3920. 1991.

34 

Pelletier JP, McCollum R, DiBattista J, Loose LD, Cloutier JM and Martel-Pelletier J: Regulation of human normal and osteo-arthritic chondrocyte interleukin-1 receptor by antirheumatic drugs. Arthritis Rheum. 36:1517–1527. 1993. View Article : Google Scholar

35 

Henrotin Y, Kurz B and Aigner T: Oxygen and reactive oxygen species in cartilage degradation: Friends or foes? Osteoarthritis Cartilage. 13:643–654. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Carlo MD Jr and Loeser RF: Increased oxidative stress with aging reduces chondrocyte survival: Correlation with intracellular glutathione levels. Arthritis Rheum. 48:3419–3430. 2003. View Article : Google Scholar

37 

Murray MM, Zurakowski D and Vrahas MS: The death of articular chondrocytes after intra-articular fracture in humans. J Trauma. 56:128–131. 2004. View Article : Google Scholar

38 

Clérigues V, Guillén MI, Gomar F and Alcaraz MJ: Haem oxygenase-1 counteracts the effects of interleukin-1β on inflammatory and senescence markers in cartilage-subchondral bone explants from osteoarthritic patients. Clin Sci (Lond). 122:239–250. 2012. View Article : Google Scholar

39 

Fernández P, Guillén MI, Gomar F and Alcaraz MJ: Expression of heme oxygenase-1 and regulation by cytokines in human osteoarthritic chondrocytes. Biochem Pharmacol. 66:2049–2052. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Villeponteau B: The heterochromatin loss model of aging. Exp Gerontol. 32:383–394. 1997. View Article : Google Scholar : PubMed/NCBI

41 

Yu S, Wang H, Davis A and Ahmed K: Consequences of CK2 signaling to the nuclear matrix. Mol Cell Biochem. 227:67–71. 2001. View Article : Google Scholar

42 

Lorenz P, Ackermann K, Simoes-Wuest P and Pyerin W: Serum-stimulated cell cycle entry of fibroblasts requires undisturbed phosphorylation and non-phosphorylation interactions of the catalytic subunits of protein kinase CK2. FEBS Lett. 448:283–288. 1999. View Article : Google Scholar : PubMed/NCBI

43 

St-Denis NA and Litchfield DW: Protein kinase CK2 in health and disease: From birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival. Cell Mol Life Sci. 66:1817–1829. 2009. View Article : Google Scholar : PubMed/NCBI

44 

Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J and Choi AM: Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest. 103:1047–1054. 1999. View Article : Google Scholar

45 

Bauer M and Bauer I: Heme oxygenase-1: Redox regulation and role in the hepatic response to oxidative stress. Antioxid Redox Signal. 4:749–758. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim KM, Sohn DH, Kim K and Park YC: Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes. Int J Mol Med 43: 1033-1040, 2019.
APA
Kim, K.M., Sohn, D.H., Kim, K., & Park, Y.C. (2019). Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes. International Journal of Molecular Medicine, 43, 1033-1040. https://doi.org/10.3892/ijmm.2018.4016
MLA
Kim, K. M., Sohn, D. H., Kim, K., Park, Y. C."Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes". International Journal of Molecular Medicine 43.2 (2019): 1033-1040.
Chicago
Kim, K. M., Sohn, D. H., Kim, K., Park, Y. C."Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes". International Journal of Molecular Medicine 43, no. 2 (2019): 1033-1040. https://doi.org/10.3892/ijmm.2018.4016
Copy and paste a formatted citation
x
Spandidos Publications style
Kim KM, Sohn DH, Kim K and Park YC: Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes. Int J Mol Med 43: 1033-1040, 2019.
APA
Kim, K.M., Sohn, D.H., Kim, K., & Park, Y.C. (2019). Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes. International Journal of Molecular Medicine, 43, 1033-1040. https://doi.org/10.3892/ijmm.2018.4016
MLA
Kim, K. M., Sohn, D. H., Kim, K., Park, Y. C."Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes". International Journal of Molecular Medicine 43.2 (2019): 1033-1040.
Chicago
Kim, K. M., Sohn, D. H., Kim, K., Park, Y. C."Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes". International Journal of Molecular Medicine 43, no. 2 (2019): 1033-1040. https://doi.org/10.3892/ijmm.2018.4016
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