Center for Bone Biology
BMP-2 Gene Expression and Bone Formation
Research Purpose
Bone morphogenetic protein 2 (BMP-2) is the most extensively studied BMP family member. BMP-2 induces osteoblast differentiation and bone formation. BMP-2 knockout mice exhibit reduced bone mass and spontaneous bone fracture, suggesting that BMP-2 is required for postnatal bone formation. Animal aging studies have shown that both BMP-2 gene expression and BMP-2 activity are decreased in bone with ages. Recently, BMP-2 was recognized as an osteoporosis-associated gene. Therefore, BMP-2 gene expression has become a target for drug discovery for bone diseases. Using a cell-based BMP-2 promoter reporter assay, we have screened compound libraries and identified several classes of small molecular weight compounds that induce BMP-2 expression in osteoblasts and stimulate bone formation. We are interested in identifying the molecular mechanisms by which these compounds activate BMP-2 transcription in bone. Through the following research projects, we will
- Determine the transcriptional mechanisms of BMP-2 gene expression in osteoblasts;
- Develop anabolic agents that stimulate BMP-2 expression and bone formation;
- Ultimately establish novel approaches for prevention and treatment of osteoporosis.
Current projects
- Gli transcriptional regulation of BMP-2 gene expression
- Microtubule assembly and BMP-2 transcription
- Mechanism of action of resveratrol on bone
- Osteoblast-specific transcription of BMP-2: Interaction of 5’ promoter region and 3’ distant ECR sequence of BMP-2 gene
- CREB transactivation of BMP-2 in bone cells
Supporting grants
- R01 AR050605 (Gregory Mundy)
Research personnel
- Gregory R Mundy, MD
- James R Edwards, PhD
- Seon-Yle Ko, PhD
- Douglas Mortlock, PhD
Research techniques
- Determine the effects of anabolic compounds on osteoblast differentiation and bone formation in vitro and in vivo
- Characterize skeletal phenotype of genetic mouse models (transgenic and knockout mice)
- Protein-DNA interaction
