|Zhang, Jian -|
|Lazarenko, Oxana -|
|Wu, Xianli -|
|Tong, Yudong -|
|Blackburn, Michael -|
|Gomez-Avecedo, Horacio -|
|Shankar, Kartik -|
|Ronis, Martin -|
|Chen, Jinran -|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 10, 2012
Publication Date: April 20, 2012
Citation: Zhang, J., Lazarenko, O.P., Wu, X., Tong, Y., Blackburn, M.L., Gomez-Avecedo, H., Shankar, K., Badger, T.M., Ronis, M.J., Chen, J. 2012. Differential effects of short term feeding of a soy protein isolate diet and estrogen treatment on bone in the pre-pubertal rat. PLoS One. 7(4):e35736. Interpretive Summary: In this study, we have utilized pre-pubertal female rats as a model and demonstrated the effects of short term feeding of soy protein isolate (SPI) on bone in comparison to the effects of 17ß-estradiol (E2). We found that SPI and E2 have different effects on bone turnover prior to puberty. Approximately half of the genes are regulated in the same direction by E2 or SPI, but in combination, SPI blocks the estrogen effects and returns the profile towards control levels. In addition, there are E2 specific and SPI specific gene changes related to regulation of bone formation. Mechanistically, soy diet activated genes located in cell surface (such as calveolin-1 gene) but E2 does not. These results indicate SPI consumption results in significant non-classical estrogenic stimulation of cancellous bone formation prior to puberty, but may have adverse effects on overall bone quality and strength at this developmental stage as a result of reduced cortical bone formation.
Technical Abstract: Beneficial effects of a soy diet on bone quality have been assumed to be due to the putative estrogenic actions of isoflavones. We studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17 beta-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a control diet with or without E2 (0.1, 1, 10 µg/kg/d), or SPI-containing diet with or without E2 (10 micro g/kg/d) for 14 days beginning on postnatal day 17. In long bones from SPI-fed rats, only cancellous bone mineral density (BMD) was increased (p<0.05), while cortical BMD was decreased accompanied with lower bone strength compared to control casein-fed rats (p<0.05). In sharp contrast, 10 micro g/kg/d E2 not only increased trabecular BMD, but also cortical BMD compared to controls. Rats treated with the combination of SPI and E2 had an intermediate bone effect. SPI increased while E2 decreased bone turnover, and increased trabecular BMD by both E2 and SPI was associated with decreased serum scleorostin levels. Microarray analysis revealed 652 genes regulated by SPI diet, 491 genes regulated by E2, and 266 genes regulated in common by both SPI diet and E2 compared to rats fed casein. The expression of caveolin-1, a protein localized in cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulated caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05). These results indicate SPI consumption results in significant non-classical estrogenic stimulation of cancellous bone formation prior to puberty, but may have adverse effects on overall bone quality and strength at this developmental stage as a result of reduced cortical bone formation.