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. Author manuscript; available in PMC: 2013 Jan 1.
Published in final edited form as: Biochim Biophys Acta. 2011 Jul 8;1824(1):133–145. doi: 10.1016/j.bbapap.2011.06.020

Figure 3. Factors regulating expression and activity of collagenases and aggrecanases in OA.

Figure 3

The expression and activity of collagenases (e. g. MMP-13 and MMP-1) and aggrecanases (e. g. ADAMTS-4 and ADAMTS-5) can be stimulated (orange boxes) or inhibited (grey boxes) by a number of inter-related mechanisms. Expression of the central transcription factor RUNX2 is increased by mechanical and pro-inflammatory stimuli, which act via HIF-2α, HDACs and Indian hedgehog. Expression of collagenolytic MMPs can also be increased in response to FGF-2 and DDR-2 signalling, and collagenase activity increased by matriptase activation of proMMP-1 and proMMP-3 zymogens and PAR-2 signalling. These catabolic stimuli can be counteracted by a variety of chondroprotective signals. For example, MMP13 expression can be reduced by the mechano-sensitive transcription factor CITED, and ADAMTS5 expression can be reduced by miR-140 and the mechano-responsive growth factor FGF-2.