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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

CITED2- mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear.

CITED2 (CBP/p300-interacting transactivator with ED-rich tail 2) is a member of the Cited family of nuclear regulators, previously known as mrg1 (melanocyte-specific gene-related gene 1). CITED2 is inducible by varying stimuli including lipopolysaccharide, hypoxia, and cytokines such as interleukin 9 and interferon gamma. Using the immortalized human chondrocyte cell line, C-28/I2, we investigated whether CITED2 could be responsive to mechanical stimuli, and if so, whether CITED2 could mediate shear-driven regulation of matrix metalloproteinase (MMP) genes. The C-28/I2 cells were cultured under flow shear at 1-20 dyn/cm2, and the role of CIT- ED2 in regulation of MMPs was examined using the plasmids encoding sense and antisense CITED2 DNA sequences. The results showed that flow shear at 5 dyn/cm2 increased CITED2 mRNA and protein levels and down-regulated MMP-1 and MMP-13 mRNA and protein levels as well as enzyme activities. Consistent with the coordinated expression patterns of CITED2 and MMPs, overexpression of CITED2 repressed MMP-1 and MMP-13 mRNA levels and activities, whereas antisense CITED2 plasmids prevented the shear-induced down-regulation of MMP expression. Interleukin-1beta induced the formation of p300-Ets-1 complexes without affecting expression of CITED2. Transforming growth factor-beta as well as flow shear at 5 dyn/cm2 stimulated not only the expression of CITED2 but also the association of CIT- ED2 with p300 by dissociating Ets-1 from p300. These results indicate that CITED2 plays a major role in shear- induced down-regulation of MMP-1 and MMP-13 via a transforming growth factor-beta-dependent pathway.[1]


  1. CITED2-mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear. Yokota, H., Goldring, M.B., Sun, H.B. J. Biol. Chem. (2003) [Pubmed]
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