CITED2 mechanoregulation of matrix metalloproteinases
- 5 April 2010
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 1192 (1), 429-436
- https://doi.org/10.1111/j.1749-6632.2009.05305.x
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
This publication has 40 references indexed in Scilit:
- Identification of CITED2 as a negative regulator of fracture healingBiochemical and Biophysical Research Communications, 2009
- Coordinate Regulation of IL-1β and MMP-13 in Rat Tendons Following Subrupture Fatigue DamageClinical Orthopaedics & Related Research, 2008
- A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasionFEBS Letters, 2007
- Anti‐inflammatory effects of continuous passive motion on meniscal fibrocartilageJournal of Orthopaedic Research, 2005
- Physical and Functional Interactions among AP-2 Transcription Factors, p300/CREB-binding Protein, and CITED2Journal of Biological Chemistry, 2003
- A central role for nuclear factor‐κB pathway in the antiinflammatory and proinflammatory actions of mechanical strainThe FASEB Journal, 2003
- MRG1 Expression in Fibroblasts Is Regulated by Sp1/Sp3 and an Ets Transcription FactorPublished by Elsevier BV ,2001
- Molecular Cloning and Chromosomal Localization of the Human CITED2 Gene Encoding p35srj/Mrg1Genomics, 1999
- Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes.JCI Insight, 1994
- Softening of Canine Articular Cartilage After Immobilization of the Knee JointPublished by Ovid Technologies (Wolters Kluwer Health) ,1986