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Sunday, March 28, 2010

COMP

Cartilage Oligomeric Matrix Protein Enhances Osteogenesis by Directly Binding and Activating Bone Morphogenetic Protein-2.

"COMP binds BMP-2, and characterized the biochemical nature of the binding interaction. COMP binding enhanced BMP-2-induced intracellular signaling through Smad proteins, increased the levels of BMP receptors, and up-regulated the luciferase activity from a BMP-2-responsive reporter construct. COMP binding enhanced BMP-2-dependent osteogenesis in vitro, in the C2C12 cell line and in primary human bone mesenchymal stem cells, as measured by alkaline phosphatase activity, matrix mineralization, and gene expression. COMP enhanced BMP-2-dependent ectopic bone formation in a rat model. COMP enhances the osteogenic activity of BMP-2, both in-vitro and in-vivo."

But can COMP enhance the chondrogenic activity of BMP-2?  "COMP prolongs BMP-2-dependent Smad activation and receptor levels."<-since BMP-2 Smad signaling can induce chondrogenesis it should.

COMP along with BMP-2 also increased Smad1/5/8 phosphorylation and increased the amount of BMP-2 receptors.

COMP did not affect TGF-Beta signaling.

"Histological analysis showed that BMP-2 application induced bone formation, as observed with the von Kossa positive mineralized matrix and a few cartilaginous masses. Co-administration of BMP-2 and COMP, enhanced the von Kossa positive areas. More Safranin-O positive chondrocytes with empty lacunae were found in BMP-2 plus COMP group, compared to the BMP-2 alone group."<-So BMP-2 and COMP did induce chondrogenesis.

"COMP interacts with aggrecan and collagens, which results in enhanced assembly and retention of the matrix during chondrogenesis in MSCs. COMP regulates endochondral bone growth via overcoming the inhibitory effect toward matrix mineralization, and endochondral bone formation by extracellular matrix protein 1 (ECM1), by interacting to ECM1."

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