Abstract 124: Using Small Molecule Screens to Identify Novel IRF6 Gene Regulatory Pathways in Orofacial Cleft Pathogenesis
نویسندگان
چکیده
Sarday, M ay 6, 2017 RESULTS: In vitro analysis of mesenchymal cells carrying the Ad.Flp/Ad.Cre construct demonstrated a significant loss in osteogenic potential (p<0.05) and pSMAD1/5 signaling in the absence of Tak1. Reactivation of Tak1 was sufficient to restore pSMAD1/5 signaling and osteogenic differentiation. Tak1 knockout demonstrated an opposite effect on cell proliferation with immediate and significant (p<0.05) increases in cell growth upon knockout and normalization of cell proliferation on gene reactivation. Loss of Tak1 in the calvarial wound environment resulted in increased presence of mesenchymal cells and increased expression of proliferative genes including Ccnd1, E2f1, and Ki67, an effect reversed by Ad.Flp reactivation of Tak1. Consistent with our in vitro data, loss of Tak1 in calvarial tissue led to diminished osteogenic differentiation genes including Bmp2, Tgfβ1, Col1, Ocn, and Runx2. Again this effect was reversed by Ad.Flp reactivation of Tak1.
منابع مشابه
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عنوان ژورنال:
دوره 5 شماره
صفحات -
تاریخ انتشار 2017