| Although the pathophysiology of HO is not well understood, it has been suggested that mesenchymal cells near surgical sites, are exposed to bone particles, containing bone morphogenetic proteins (BMP). Fetuin, also known as alpha2HS-glycoprotein (Ahsg), is a serum glycoprotein, which binds TGFbeta and BMP cytokines due its BMP/TGFbeta receptor-like region within the fetuin structure. We hypothesize that the osteodifferentiation of C2C12 cells under the influence of BMPs will be inhibited by fetuin. Mouse myoblasts were grown with BMP and fetuin added to the media. There was an increase AP activity in the presence of increasing doses of BMP/NCP or rhBMP-4. Fetuin inhibited induced increases in AP in a dose-dependent fashion with the most effective dose being in the range of 50--80muM fetuin. C2C12 cultures exhibited increased CK expression with the addition of 20ng/ml of rBMP-4. This increase was similarly inhibited by approximately 50muM fetuin. Using this model, fetuin has been shown to inhibit the effects of BMPs on target cells. As well, using this model we were able to approximate the doses of fetuin that might be required for regulation of BMP effects in vivo. |
