RRC ID 45017
Author Zhang J, Lazarenko OP, Blackburn ML, Badger TM, Ronis MJ, Chen JR.
Title Soy protein isolate down-regulates caveolin-1 expression to suppress osteoblastic cell senescence pathways.
Journal FASEB J.
Abstract It has been suggested that the beneficial effects of soy protein isolate (SPI) on bone quality are due to either stimulation of estrogenic signaling via isoflavones or through a novel and as yet uncharacterized nonestrogenic pathway. In our study, SPI-fed rat serum inhibited the osteoblastic cell senescence pathway. This effect was accompanied by stimulation of cell differentiation, proliferation, and significant restoration of replicative senescent bone marrow mesenchymal ST2 cells (passaged 30 times). These effects were reproduced in bone from 5-wk-old intact and 10-wk-old ovariectomized female rats fed SPI diets. Caveolin-1 and p53 expression was decreased in bone in SPI-fed, but not in 17β-estradiol (E2)-treated rats. In cell culture studies, membranous caveolin-1 and nuclear p53 expression was greater in replicative senescent ST2 cell cultures than in earlier passaged cells. SPI-fed rat serum significantly down-regulated both caveolin-1 and p53 in senescent and nonsenescent cells. Replicative senescent ST2 cells exhibited a strong association among caveolin-1, p53, and mouse double minute 2 homologue (mdm2), which was inhibited by SPI-fed rat serum. Overexpression of caveolin-1 in ST2 cells resulted in increased expression of p53 and p21, whereas, knockdown of caveolin-1 using shRNA led to increases in mdm2 and eliminated SPI-fed rat serum's 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 of nonestrogenic SPI effects on bone cells.-Zhang, J., Lazarenko, O. P., Blackburn, M. L., Badger, T. M., Ronis, M. J. J., Chen, J.-R. Soy protein isolate down-regulates caveolin-1 expression to suppress osteoblastic cell senescence pathways.
Volume 28(7)
Pages 3134-45
Published 2014-7
DOI 10.1096/fj.13-243659
PII fj.13-243659
PMID 24719353
MeSH Animals Bone and Bones / metabolism Caveolin 1 / genetics* Caveolin 1 / metabolism Cell Differentiation / genetics Cell Line Cell Proliferation Cellular Senescence / genetics* Down-Regulation / genetics* Female Mesenchymal Stem Cells / metabolism Mice Osteoblasts / metabolism* Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 / metabolism Rats Rats, Sprague-Dawley Signal Transduction / genetics* Soybean Proteins / metabolism* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism
IF 5.391
Times Cited 7
Human and Animal Cells