Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2014 Volume 34 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2014 Volume 34 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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
  • View Affiliations / Copyright

    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
  • Pages: 1335-1340
    |
    Published online on: August 29, 2014
       https://doi.org/10.3892/ijmm.2014.1918
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Salminen A, Ojala J and Kaarniranta K: Apoptosis and aging: increased resistance to apoptosis enhances the aging process. Cell Mol Life Sci. 68:1021–1031. 2011. View Article : Google Scholar : PubMed/NCBI

2 

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 : PubMed/NCBI

3 

Horton WE Jr, Feng L and Adams C: Chondrocyte apoptosis in development, aging and disease. Matrix Biol. 17:107–115. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Kühn K, D’Lima DD, Hashimoto S and Lotz M: Cell death in cartilage. Osteoarthritis Cartilage. 12:1–16. 2004.

5 

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

6 

Martin JA and Buckwalter JA: Telomere erosion and senescence in human articular cartilage chondrocytes. J Gerontol A Biol Sci Med Sci. 56:B172–B179. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Aigner T, Hemmel M, Neureiter D, Gebhard PM, Zeiler G, Kirchner T and McKenna L: Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum. 44:1304–1312. 2001.

8 

Hashimoto S, Ochs RL, Komiya S and Lotz M: Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. 41:1632–1638. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Blanco FJ, Guitian R, Vázquez-Martul E, de Toro FJ and Galdo F: Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 41:284–289. 1998. View Article : Google Scholar : PubMed/NCBI

10 

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

11 

Muller M: Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal. 11:59–98. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Taketani S, Kohno H, Yoshinaga T and Tokunaga R: The human 32-kDa stress protein induced by exposure to arsenite and cadmium ions is heme oxygenase. FEBS Lett. 245:173–176. 1989. View Article : Google Scholar : PubMed/NCBI

13 

Keyse SM and Tyrrell RM: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblast by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci USA. 86:99–103. 1989. View Article : Google Scholar : PubMed/NCBI

14 

Durante W, Kroll MH, Christodoulides N, Peyton KJ and Schafer AI: Nitric oxide induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle cells. Circ Res. 80:557–564. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Valvason C, Musacchio E, Pozzuoli A, Ramonda R, Aldegheri R and Punzi L: Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22(Phox) and iNOS expression. Rheumatology (Oxford). 47:31–35. 2008. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Eyre D: Collagen of articular cartilage. Arthritis Res. 4:30–35. 2002. View Article : Google Scholar

18 

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

19 

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

20 

Kim KM, Kim JM, Yoo YH, Kim JI and Park YC: Cilostazol induces cellular senescence and confers resistance to etoposide-induced apoptosis in articular chondrocytes. Int J Mol Med. 29:619–624. 2012.PubMed/NCBI

21 

Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 92:9363–9367. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Lee SY, Jo HJ, Kim KM, Song JD, Chung HT and Park YC: Concurrent expression of heme oxygenase-1 and p53 in human retinal pigment epithelial cell line. Biochem Biophy Res Commun. 365:870–874. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Vincenti MP, Coon CI, Lee O and Brinckerhoff CE: Regulation of collagenase gene expression by IL-1 beta requires transcriptional and post-transcriptional mechanisms. Nucleic Acids Res. 22:4818–4827. 1994. View Article : Google Scholar : PubMed/NCBI

24 

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

25 

Goldring MB: Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep. 2:459–465. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Wilks A: Heme oxygenase: evolution, structure, and mechanism. Antioxid Redox Signal. 4:603–614. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Otterbein LE and Choi AM: Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol. 279:L1029–L1037. 2000.PubMed/NCBI

28 

Duckers HJ, Boehm M, True AL, Yet S-F, San H, Park JL, Webb RC, Lee M-E, Nabel GJ and Nabel EG: Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med. 7:693–698. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Pae HO, Choi BM, Oh GS, Lee MS, Ryu DG, Rhew HY, Kim YM and Chung HT: Roles of heme oxygenase-1 in the antiproliferative and antiapoptotic effects of nitric oxide on Jurkat T cells. Mol Pharmacol. 66:122–128. 2004. View Article : Google Scholar : PubMed/NCBI

30 

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.PubMed/NCBI

31 

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.PubMed/NCBI

32 

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

33 

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 : PubMed/NCBI

34 

Kim HA, Lee KB and Bae S-C: The mechanism of low-concentration sodium nitroprusside-mediated protection of chondrocyte death. Arthritis Res Ther. 7:R526–R535. 2005. View Article : Google Scholar : PubMed/NCBI

35 

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

36 

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 : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
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.
APA
Kim, K.M., Park, S.E., Lee, M.S., Kim, K., & Park, Y.C. (2014). Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence. International Journal of Molecular Medicine, 34, 1335-1340. https://doi.org/10.3892/ijmm.2014.1918
MLA
Kim, K. M., Park, S. E., Lee, M. S., Kim, K., Park, Y. C."Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence". International Journal of Molecular Medicine 34.5 (2014): 1335-1340.
Chicago
Kim, K. M., Park, S. E., Lee, M. S., Kim, K., Park, Y. C."Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence". International Journal of Molecular Medicine 34, no. 5 (2014): 1335-1340. https://doi.org/10.3892/ijmm.2014.1918
Copy and paste a formatted citation
x
Spandidos Publications style
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.
APA
Kim, K.M., Park, S.E., Lee, M.S., Kim, K., & Park, Y.C. (2014). Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence. International Journal of Molecular Medicine, 34, 1335-1340. https://doi.org/10.3892/ijmm.2014.1918
MLA
Kim, K. M., Park, S. E., Lee, M. S., Kim, K., Park, Y. C."Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence". International Journal of Molecular Medicine 34.5 (2014): 1335-1340.
Chicago
Kim, K. M., Park, S. E., Lee, M. S., Kim, K., Park, Y. C."Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence". International Journal of Molecular Medicine 34, no. 5 (2014): 1335-1340. https://doi.org/10.3892/ijmm.2014.1918
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team