Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes

Yung-Cheng Chiu, Rong-Sen Yang, Kuo-Hsien Hsieh, Yi-Chin Fong, Tzong-Der Way, Tu-Sheng Lee, Hsi-Chin Wu, Wen-Mei Fu and Chih-Hsin Tang
Molecular Pharmacology September 2007, 72 (3) 695-703; DOI: https://doi.org/10.1124/mol.107.036541
Yung-Cheng Chiu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rong-Sen Yang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kuo-Hsien Hsieh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi-Chin Fong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tzong-Der Way
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tu-Sheng Lee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hsi-Chin Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wen-Mei Fu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chih-Hsin Tang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The production of chemokine stromal cell-derived factor (SDF)-1 is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of articular cartilage during arthritis. Here, we found that SDF-1α increased the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse transcriptase-polymerase chain reaction, Western blot, and zymographic analysis. SDF-1α also increased the surface expression of CXCR4 receptor in human chondrocytes. CXCR4-neutralizing antibody, CXCR4-specific inhibitor [1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane (AMD3100)], or small interfering RNA against CXCR4 inhibited the SDF-1α-induced increase of MMP-13 expression. The transcriptional regulation of MMP-13 by SDF-1α was mediated by phosphorylation of extracellular signal-regulated kinases (ERK) and activation of the activator protein (AP)-1 components of c-Fos and c-Jun. The binding of c-Fos and c-Jun to the activator protein (AP-1) element on the MMP-13 promoter and the increase in luciferase activity was enhanced by SDF-1α. Cotransfection with dominant-negative mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide inhibited the potentiating action of SDF-1α on MMP-13 promoter activity. Taken together, our results provide evidence that SDF-1α acts through CXCR4 to activate ERK and the downstream transcription factors (c-Fos and c-Jun), resulting in the activation of AP-1 on the MMP-13 promoter and contributing cartilage destruction during arthritis.

Footnotes

  • This work was supported by a grant from Taichung Veterans General Hospital (TCVGH-TTMHH968501) and National Science Council.

  • Y.-C.C., R.-S.Y., and K.-H.H. contributed equally to this work. C.-H.T. and W.-M.F. contributed equally to this work.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

  • doi:10.1124/mol.107.036541.

  • ABBREVIATIONS: MMP, matrix metalloproteinase; OA, osteoarthritis; RA, rheumatoid arthritis; SDF, stromal cell-derived factor; SF, synovial fluid; RT-PCR, reverse transcription-polymerase chain reaction; PCR, polymerase chain reaction; Akt, protein kinase B; ERK, extracellular signalregulated kinase(s); AP, activator protein; p-, phosphorylated; JNK, c-Jun NH2-terminal kinase; PD98059, 2′-amino-3′-methoxyflavone; SB203580, 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole; SP600125, anthra(1,9-cd)pyrazol-6(2H)-one; Ly294002, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; PBS, phosphate-buffered saline; ODN, oligonucleotide; AS, antisense; MS, missense; ChIP, chromatin immunoprecipitation; MAPK, mitogen-activated protein kinase; TNF, tumor necrosis factor; si, small interfering, mut, mutated.

    • Received March 28, 2007.
    • Accepted June 4, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 72 (3)
Molecular Pharmacology
Vol. 72, Issue 3
1 Sep 2007
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes

Yung-Cheng Chiu, Rong-Sen Yang, Kuo-Hsien Hsieh, Yi-Chin Fong, Tzong-Der Way, Tu-Sheng Lee, Hsi-Chin Wu, Wen-Mei Fu and Chih-Hsin Tang
Molecular Pharmacology September 1, 2007, 72 (3) 695-703; DOI: https://doi.org/10.1124/mol.107.036541

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Stromal Cell-Derived Factor-1 Induces Matrix Metalloprotease-13 Expression in Human Chondrocytes

Yung-Cheng Chiu, Rong-Sen Yang, Kuo-Hsien Hsieh, Yi-Chin Fong, Tzong-Der Way, Tu-Sheng Lee, Hsi-Chin Wu, Wen-Mei Fu and Chih-Hsin Tang
Molecular Pharmacology September 1, 2007, 72 (3) 695-703; DOI: https://doi.org/10.1124/mol.107.036541
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
  • Positive allosteric modulation of the mGlu5 receptor
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics