CITED2 mechanoregulation of matrix metalloproteinases

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

9 Citations (Scopus)

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 publicationAnnals of the New York Academy of Sciences
Pages429-436
Number of pages8
Volume1192
DOIs
StatePublished - Mar 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Matrix Metalloproteinases
Cartilage
Joints
Tissue
Degradation
Trans-Activators
Articular Cartilage
Chondrocytes
Homeostasis
Switches

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

CITED2 mechanoregulation of matrix metalloproteinases. / Sun, Hui (Herb).

Annals of the New York Academy of Sciences. Vol. 1192 2010. p. 429-436 (Annals of the New York Academy of Sciences; Vol. 1192).

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

Sun, HH 2010, CITED2 mechanoregulation of matrix metalloproteinases. in Annals of the New York Academy of Sciences. vol. 1192, Annals of the New York Academy of Sciences, vol. 1192, pp. 429-436. https://doi.org/10.1111/j.1749-6632.2009.05305.x
Sun HH. CITED2 mechanoregulation of matrix metalloproteinases. In Annals of the New York Academy of Sciences. Vol. 1192. 2010. p. 429-436. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.05305.x
Sun, Hui (Herb). / CITED2 mechanoregulation of matrix metalloproteinases. Annals of the New York Academy of Sciences. Vol. 1192 2010. pp. 429-436 (Annals of the New York Academy of Sciences).
@inproceedings{dcc084ccd1084dc88d4b803f1963a6e3,
title = "CITED2 mechanoregulation of matrix metalloproteinases",
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.",
keywords = "CITED2, Ets-1, Matrix metalloproteinases, Mechanical loading, Mechanoregulation, P300",
author = "Sun, {Hui (Herb)}",
year = "2010",
month = "3",
doi = "10.1111/j.1749-6632.2009.05305.x",
language = "English (US)",
isbn = "9781573317856",
volume = "1192",
series = "Annals of the New York Academy of Sciences",
pages = "429--436",
booktitle = "Annals of the New York Academy of Sciences",

}

TY - GEN

T1 - CITED2 mechanoregulation of matrix metalloproteinases

AU - Sun, Hui (Herb)

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

KW - CITED2

KW - Ets-1

KW - Matrix metalloproteinases

KW - Mechanical loading

KW - Mechanoregulation

KW - P300

UR - http://www.scopus.com/inward/record.url?scp=77950658717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950658717&partnerID=8YFLogxK

U2 - 10.1111/j.1749-6632.2009.05305.x

DO - 10.1111/j.1749-6632.2009.05305.x

M3 - Conference contribution

C2 - 20392269

AN - SCOPUS:77950658717

SN - 9781573317856

VL - 1192

T3 - Annals of the New York Academy of Sciences

SP - 429

EP - 436

BT - Annals of the New York Academy of Sciences

ER -