Location: Arkansas Children's Nutrition CenterTitle: Soy protein isolate down-regulates caveolin-1 expression to suppress osteoblastic cell senescence pathways) Author
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2014
Publication Date: 7/1/2014
Citation: Zhang, J., Lazarenko, O.P., Vlxkvuen, M.L., Badger, T.M., Ronis, M.J., Chen, J. 2014. Soy protein isolate down-regulates caveolin-1 expression to suppress osteoblastic cell senescence pathways. FASEB Journal. 28(7):3134-3145. Interpretive Summary: We know that proteins isolated from soy (SPI) contain compounds like the female sex steroid estrogen, and they are called isoflavones. Beneficial effects of SPI diet on bone quality has been suggested previously as either due to isoflavones or through novel and as yet uncharacterized new compounds. We report here that SPI-containing diet and estrogen both had positive effects on bone quality. Both SPI diet and estrogen were able to prevent skeletal aging, but acted in different mechanisms. SPI diet down-regulated caveolin-1 and p53 gene expression (mRNA and protein), but estrogen did not affect caveolin-1 gene expression in bone and bone-forming cells. These results suggest that caveolin-1 is a mediator for the new SPI actions on bone cells.
Technical Abstract: It has been suggested that the beneficial effects of soy protein isolate (SPI) on bone quality might be due to either stimulation of estrogenic signaling via isoflavones or through a novel and as yet characterized non-estrogenic pathway. We report here that SPI-fed rat serum inhibited osteoblastic cell senescence pathway. This was accompanied by stimulation of cell differentiation, proliferation, and significant restoration of replicative senescent bone marrow mesenchymal ST2 cells (cells passaged 30 times). These effects were reproduced in bone from 1-mo-old intact and 4-mo-old ovariectomized (OVX) female rats fed SPI diets. Caveolin-1 and p53 expression was decreased in bone in SPI-fed, but not in 17beta-estradiol (E2)-treated rats. In cell culture studies, membranous caveolin-1 and nuclear p53 expression was greater in replicative senescent ST2 cell cultures compared to earlier passaged cells. SPI-fed rat serum significantly down-regulated both caveolin-1 and p53 in senescent and non-senescent cells. Replicative senescent ST2 cells exhibited a strong association among caveolin-1, p53, and mdm2, which was inhibited by SPI-fed rat serum. Over expression of caveolin-1 in ST2 cells resulted in increased expression of p53 and p21; whereas, knockdown of caveolin-1 using shRNA led to increases of mdm2 and eliminated SPI-fed rat serum effects on p53 and p21 expression. In contrast, manipulation of caveolin-1 expression did not affect the actions of E2 or isoflavones on p53 expression in either ST2 or OB6 cells. These results suggest that caveolin-1 is a mediator for the non-estrogenic SPI actions on bone cells.