"CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) [is] a mechanosensitive transcriptional coregulator. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1[LSJL upregulates TIMP1 which inhibits MMP-1] and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. CITED2 suppresses MMP-1 expression[and MMP-13 expression] by competing with MMP transactivator, Ets-1 for its coactivator p300. CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP."
"the application of 2.5 and 5.0 MPa, pressures consistent with those experienced by joints during walking, caused a profound increase in CITED2 and a decrease in MMP-1 mRNA expression in rat articular cartilage explants"
"chondrocytes loaded at 10 MPa resulted in the phosphorylation of p38α, which coincides with the up-regulation of MMP-1"
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