Abstract
The forkhead box transcription factor FOXC1 is necessary for bone morphogenetic protein (BMP)‐mediated induction of early skeletogenic patterning events. We hypothesize that FOXC1 and SMAD proteins interact to regulate BMP signalling necessary for normal skeletal development. First we demonstrate that FOXC1 and SMAD5 physically interact through co‐immunoprecipitation experiments. Next we show that BMP2 enhances activation of a FOXC1‐responsive reporter gene. We tested whether FOXC1 could mediate signalling of a BMP2‐responsive reporter (2xBRE‐luc). We find that on its own, FOXC1 has no affect on activation of 2xBRE‐luc. Surprisingly, when BMP2 is added, FOXC1 inhibits activation of this reporter. Moreover, FOXC1 prevents activation of this BMP‐responsive element when SMAD4 and SMAD5 are co‐transfected along with FOXC1. To test whether FOXC1 impacted BMP2 mediated osteogenic differentation, we created C2C12 cell lines stably expressing FOXC1. We find that cells expressing FOXC1 differentiated into alkaline phosphatase‐positive osteoblasts in the absence BMP2, yet treatment of FOXC1 expressing cells with BMP2 led to no appreciable increase in alkaline phosphatase activity. Finally we show that FOXC1 prevents activation of Runx2 expression by BMP2. Together these data indicate that FOXC1 and SMAD5 proteins interact to regulate BMP‐signalling in a context dependent manner.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.