Abstract
Osteoporosis is a major public health problem and the most obvious preventive strategy, hormone replacement therapy, has lost favor due to recent findings of the Women's Health Initiative regarding increased risks of breast cancer and cardiovascular disease. Resveratrol, a naturally occurring compound possessing estrogenic activity, is thought to have considerable potential for therapy of osteoporosis. In the present study, resveratrol was found to exhibit bone-protective effects equivalent to those exerted by hormone replacement therapy and decrease the risk of breast cancer in the in vivo and in vitro models. Forkhead proteins were found to be essential for both effects of resveratrol. The bone-protective effect was attributable to induction of bone morphogenetic protein-2 through Src kinase-dependent estrogen receptor activation and FOXA1 is required for resveratrol-induced estrogen receptor-dependent bone morphogenetic protein-2 expression. The tumor-suppressive effects of resveratrol were the consequence of Akt inactivation-mediated FOXO3a nuclear accumulation and activation. Resveratrol is therefore anticipated to be highly effective in management of postmenopausal osteoporosis without an increased risk of breast cancer.
Highlights
Osteoporosis is a major public health concern and is especially troublesome for menopausal and postmenopausal females who suffer from estrogen deficiency
It is widely believed that osteoporosis results from imbalance between bone resorption and bone formation leading to net bone loss [1]
Our results provide the evidences to show the phytoestrogen, resveratrol, would be a critical strategy for a therapeutic or preventive intervention for bone loss without increase the breast cancer risk through the regulation of forkhead proteins
Summary
Antibodies and Reagents—Anti-BMP-2 antibody, anti--actin antibody, BMP-2 ELISA kit, osteopontin ELISA kit, and noggin were obtained from R&D Systems (Minneapolis, MN). The culture medium was collected and measured for osteocalcin, osteopontin, and BMP-2, respectively These samples were placed in 96-well microtiter plates coated with monoclonaldetective antibodies and incubated for 2 h at room temperature. GEArray Q series Mouse Osteogenesis Gene Array is designed to profile gene expression in the process of osteogenic differentiation The genes regulating this process include growth factors and their internal cell signaling molecules, as well as the early and later differentiation genes. Electrophoretic mobility shift assay for DNA binding in MC3T3-E1 cells was performed using the probe purchased from Santa Cruz Biotechnology and [␣-32P]dCTP end-labeled in a 20-l reaction mixture for 20 min at room temperature. After reverse transcription reaction (20 l) using 2 g of total RNA, real-time PCR was carried out in a 20-l final volume using the LightCycler-FastStart DNA Master SYBR Green I kit (Roche Applied Science).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
