Saturday, May 23, 2009


MT1-MMP-Dependent Control of Skeletal Stem Cell Commitment via a β1-Integrin/YAP/TAZ Signaling Axis.

"conditional deletion of the membrane-anchored metalloproteinase MT1-MMP (Mmp14){so inhibiting MMP14 could be one way to induce chondrogenesis?} in mesenchymal progenitors, but not in committed osteoblasts, redirects SSC fate decisions from osteogenesis to adipo- and chondrogenesis. By effecting ECM remodeling, MT1-MMP regulates stem cell shape, thereby activating a β1-integrin/RhoGTPase signaling cascade and triggering the nuclear localization of the transcriptional coactivators YAP and TAZ, which serve to control SSC lineage commitment. These data identify a critical MT1-MMP/integrin/YAP/TAZ axis operative in the stem cell niche that oversees SSC fate determination."

Illustration of how MMP14 may inhibit chondrogenesis:

Full-size image (36 K)
However MMP14 knockout results in defects including death.

" commitment to either the adipogenic or chondrogenic pathways results in decreased MT1-MMP expression"  Despite this the conditional MMP14 knockout mice seemed to develop some defects in terms of body height.

"MT1-MMP knockout transgenic mice engineered to overexpress MT1-MMP in chondrocytes to [are unable to] resorb the expanded cartilage network "

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