CREB (cAMP responsive element-binding protein) is known to be involved in a variety of intracellular signaling pathways in skeleton. We found that CREB stimulates BMP-2 gene expression in both osteoblast and chondrocytes. We hypothesize that CREB regulates BMP-2 promoter activity through CREs (cAMP responsive elements) in the promoter. Characterizing skeletal phenotype of CREB KO mice, we found that CREB deletion results in skeletal defects. Therefore, in this project we will focus on the molecular mechanisms for CREB regulation of BMP-2 in bone cells, particularly will identify the potential CRE responsible for CREB action on BMP-2 gene. We are now also generating a conditional KO mouse model, Col1a1-Cre;CREBfl/fl and ColI-Cre;CREBfl/fl, which are osteoblast- and chondrocyte-specific. With these KO models, we are able to fully characterize the function of CREB in bone.

The VUMC Center for Bone Biology is a member of the VUMC Department of Medicine in the Division of Clinical Pharmacology.