CITED2 mechanoregulation of matrix metalloproteinases

Hui B. Sun

Research output: Chapter in Book/Report/Conference proceedingConference contribution

9 Scopus citations

Abstract

Joint tissues are exquisitely sensitive to their mechanical environment. Indeed, mechanical loading may be the most important external factor regulating the development and long-term maintenance of joint tissues. Moderate mechanical loading maintains the integrity of articular cartilage, and under these conditions of homeostasis, matrix metalloproteinases (MMPs) are expressed at modest levels. However, both disuse and overuse can result in altered likely high levels of MMP expression, leading to cartilage degradation. The transcriptional regulator ED-rich tail 2 (CITED2) is expressed in chondrocytes in a load-dependent manner but in a pattern inversely related to that of MMPs. CITED2 mediates the moderate load-induced suppression of MMPs, possibly by competing with Ets-1, a known MMP transactivator, for binding to the co-activator p300, suggesting a mechanism for transcriptional suppression by CITED2. These findings suggest that CITED2 may act as a mechanosensitive molecular switch regulating cartilage matrix breakdown. This regulatory pathway could be exploited clinically to limit pathologic cartilage degradation.

Original languageEnglish (US)
Title of host publicationSkeletal Biology and Medicine
PublisherBlackwell Publishing Inc.
Pages429-436
Number of pages8
ISBN (Print)9781573317856
DOIs
StatePublished - Mar 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • CITED2
  • Ets-1
  • Matrix metalloproteinases
  • Mechanical loading
  • Mechanoregulation
  • P300

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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  • Cite this

    Sun, H. B. (2010). CITED2 mechanoregulation of matrix metalloproteinases. In Skeletal Biology and Medicine (pp. 429-436). (Annals of the New York Academy of Sciences; Vol. 1192). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.05305.x