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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2015 Volume 12 Issue 1

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
July-2015 Volume 12 Issue 1

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 Open Access

Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling

  • Authors:
    • Guangye Wang
    • Xiaohai Zhang
    • Baoqing Yu
    • Ke Ren
  • View Affiliations / Copyright

    Affiliations: The Third Department of Orthopaedics, Wuhu Second People's Hospital, Wuhu, Anhui 241000, P.R. China, Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Centre, Shanghai 201399, P.R. China, Department of Orthopedics, Nanjing General Hospital of Nanjing Military Command Region, Nanjing, Jiangsu 210002, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 877-884
    |
    Published online on: March 20, 2015
       https://doi.org/10.3892/mmr.2015.3524
  • 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

The differentiation of pluripotent mesenchymal stem cells to mature osteoblasts is crucial for the maintenance of the adult skeleton. In rheumatic arthritis, osteoblast differentiation is impaired by the overproduction of cytokine tumor necrosis factor (TNF)‑α. It has been demonstrated that TNF‑α is able to inhibit osteoblast differentiation through the activation of nuclear factor (NF)‑κB signaling. As a result of the critical role of TNF‑α and NF‑κB in the pathogenesis of bone‑loss associated diseases, these factors are regarded as key targets for the development of therapeutic agents. In the current study, the role of the NF‑κB inhibitor gliotoxin (GTX) in the regulation of osteoblast differentiation was evaluated. The non‑toxic GTX doses were determined to be ≤3 µg/ml. It was revealed that GTX was able to block TNF‑α‑induced inhibition of osteoblast differentiation, as indicated by alkaline phosphatase (ALP) activity and ALP staining assays, as well as the expression levels of osteoblast‑associated genes Col I, Ocn, Bsp, Runx2, Osx and ATF4. Additionally, it was identified that gliotoxin directly promoted bone morphogenetic protein‑2‑induced osteoblast differentiation. GTX was found to inhibit the accumulation of NF‑κB protein p65 in the nucleus and reduce NF‑κB transcriptional activity, suggesting that GTX potentiated osteoblast differentiation via the suppression of NF-κB signaling.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Uccelli A, Moretta L and Pistoia V: Mesenchymal stem cells in health and disease. Nat Rev Immunol. 8:726–736. 2008. View Article : Google Scholar

2 

Zaidi M: Skeletal remodeling in health and disease. Nat Med. 13:791–801. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Huang W, Yang S, Shao J and Li YP: Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci. 12:3068–3092. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Karsenty G, Kronenberg HM and Settembre C: Genetic control of bone formation. Annu Rev Cell Dev Biol. 25:629–648. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Baum R and Gravallese EM: Impact of inflammation on the osteoblast in rheumatic diseases. Curr Osteoporos Rep. 12:9–16. 2014. View Article : Google Scholar :

6 

Walsh NC and Gravallese EM: Bone remodeling in rheumatic disease: a question of balance. Immunol Rev. 233:301–312. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Walsh NC, Reinwald S, Manning CA, et al: Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res. 24:1572–1585. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Cenci S, Weitzmann MN, Roggia C, et al: Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest. 106:1229–1237. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Roggia C, Gao Y, Cenci S, et al: Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci USA. 98:13960–13965. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Canalis E: Effects of tumor necrosis factor on bone formation in vitro. Endocrinology. 121:1596–1604. 1987. View Article : Google Scholar : PubMed/NCBI

11 

Gilbert L, He X, Farmer P, et al: Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology. 141:3956–3964. 2000.PubMed/NCBI

12 

Li Y, Li A, Strait K, Zhang H, Nanes MS and Weitzmann MN: Endogenous TNFalpha lowers maximum peak bone mass and inhibits osteoblastic Smad activation through NF-kappaB. J Bone Miner Res. 22:646–655. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Chang J, Wang Z, Tang E, et al: Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat Med. 15:682–689. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Locksley RM, Killeen N and Lenardo MJ: The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 104:487–501. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Dempsey PW, Doyle SE, He JQ and Cheng G: The signaling adaptors and pathways activated by TNF superfamily. Cytokine Growth Factor Rev. 14:193–209. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Novack DV: Role of NF-κB in the skeleton. Cell Res. 21:169–182. 2011. View Article : Google Scholar

17 

Kular J, Tickner J, Chim SM and Xu J: An overview of the regulation of bone remodelling at the cellular level. Clin Biochem. 45:863–873. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Raggatt LJ and Partridge NC: Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 285:25103–25108. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Xu J, Wu HF, Ang ES, et al: NF-kappaB modulators in osteolytic bone diseases. Cytokine Growth Factor Rev. 20:7–17. 2009. View Article : Google Scholar

20 

Scharf DH, Heinekamp T, Remme N, Hortschansky P, Brakhage AA and Hertweck C: Biosynthesis and function of gliotoxin in Aspergillus fumigatus. Appl Microbiol Biotechnol. 93:467–472. 2012. View Article : Google Scholar

21 

Kupfahl C, Ruppert T, Dietz A, Geginat G and Hof H: Candida species fail to produce the immunosuppressive secondary metabolite gliotoxin in vitro. FEMS Yeast Res. 7:986–992. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Kosalec I, Puel O, Delaforge M, et al: Isolation and cytotoxicity of low-molecular-weight metabolites of Candida albicans. Front Biosci. 13:6893–6904. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Sutton P, Newcombe NR, Waring P and Müllbacher A: In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human pathogenic fungi. Infect Immun. 62:1192–1198. 1994.PubMed/NCBI

24 

Pahl HL, Krauss B, Schulze-Osthoff K, et al: The immuno-suppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB. J Exp Med. 183:1829–1840. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Kroll M, Arenzana-Seisdedos F, Bachelerie F, Thomas D, Friguet B and Conconi M: The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome. Chem Biol. 6:689–698. 1999. View Article : Google Scholar : PubMed/NCBI

26 

López-Franco O, Suzuki Y, Sanjuán G, et al: Nuclear factor-kappa B inhibitors as potential novel anti-inflammatory agents for the treatment of immune glomerulonephritis. Am J Pathol. 161:1497–1505. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Karin M: Nuclear factor-kappaB in cancer development and progression. Nature. 441:431–436. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Hur JM, Yun HJ, Yang SH, Lee WY, Joe MH and Kim D: Gliotoxin enhances radiotherapy via inhibition of radiation-induced GADD45a, p38 and NFkappaB activation. J Cell Biochem. 104:2174–2184. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Goldring SR and Gravallese EM: Pathogenesis of bone erosions in rheumatoid arthritis. Curr Opin Rheumatol. 12:195–199. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Krum SA, Chang J, Miranda-Carboni G and Wang CY: Novel functions for NFkappaB: inhibition of bone formation. Nat Rev Rheumatol. 6:607–611. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Soysa NS and Alles N: NF-kappaB functions in osteoclasts. Biochem Biophys Res Commun. 378:1–5. 2009. View Article : Google Scholar

32 

Ozaki K, Takeda H, Iwahashi H, Kitano S and Hanazawa S: NF-kappaB inhibitors stimulate apoptosis of rabbit mature osteoclasts and inhibit bone resorption by these cells. FEBS Lett. 410:297–300. 1997. View Article : Google Scholar : PubMed/NCBI

33 

Trebec-Reynolds DP, Voronov I, Heersche JN and Manolson MF: VEGF-A expression in osteoclasts is regulated by NF-kappaB induction of HIF-1alpha. J Cell Biochem. 110:343–351. 2010.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang G, Zhang X, Yu B and Ren K: Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling. Mol Med Rep 12: 877-884, 2015.
APA
Wang, G., Zhang, X., Yu, B., & Ren, K. (2015). Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling. Molecular Medicine Reports, 12, 877-884. https://doi.org/10.3892/mmr.2015.3524
MLA
Wang, G., Zhang, X., Yu, B., Ren, K."Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling". Molecular Medicine Reports 12.1 (2015): 877-884.
Chicago
Wang, G., Zhang, X., Yu, B., Ren, K."Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling". Molecular Medicine Reports 12, no. 1 (2015): 877-884. https://doi.org/10.3892/mmr.2015.3524
Copy and paste a formatted citation
x
Spandidos Publications style
Wang G, Zhang X, Yu B and Ren K: Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling. Mol Med Rep 12: 877-884, 2015.
APA
Wang, G., Zhang, X., Yu, B., & Ren, K. (2015). Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling. Molecular Medicine Reports, 12, 877-884. https://doi.org/10.3892/mmr.2015.3524
MLA
Wang, G., Zhang, X., Yu, B., Ren, K."Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling". Molecular Medicine Reports 12.1 (2015): 877-884.
Chicago
Wang, G., Zhang, X., Yu, B., Ren, K."Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-κB signaling". Molecular Medicine Reports 12, no. 1 (2015): 877-884. https://doi.org/10.3892/mmr.2015.3524
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