Fan Z et al. - This study illustrates the complex regulation of MMP-13 by showing the inhibitory effect of the two cytoplasmic molecules, p130cas and Hsp90β in L-OA chondrocytes. Methods
Study to (i) identify regulators of MMP-13 expression/production in human L-OA chondrocytes, (ii) determine their effect on the expression of other MMPs and the effect of IL-1β on these molecules
identification of the L-OA chondrocyte proteins interacting with the MMP-13 promoter AGRE-site was performed by mass spectrometry
Hsp90β, p130cas and NMP4 siRNAs were transfected into L-OA chondrocytes and incubated with or w/o IL-1β
Gene expression was determined by RT-PCR, MMP-1 and -13 production by ELISA ; signaling pathway activation by Western blotting and ELISA
Results
Hsp90β was identified as a protein of the L-OA/AGRE specific complex
Silencing p130cas and Hsp90β increased the expression and production of MMP-13
sip130cas affected to a lesser extent MMP-1 expression and production; siNMP4 showed no effect
MMP-2, -3, -9 and -14 expressions were unaffected
Silencing both Hsp90β and p130cas had a significant additive effect on MMP-13, but not MMP-1 expression
IL-1β decreased p130cas and Hsp90β expression/production, indicating another pathway by which this cytokine up-regulates MMP expression
The IL-1β-triggered signaling pathways responsible for MMP up-regulation were unaffected in the silenced cells
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