Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Blueberry Diets during Early Development Only Is Sufficient to Prevent Senescence of Osteoblasts and Bone Loss in Adulthood

ABSTRACT: Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we have demonstrated several fundamental issues in the field. 1) A significant prevention of ovariectomy (OVX) -induced bone loss from adult rats can occur with only 14 days consumption of a blueberry-containing diet immediately prior to puberty. 2) The molecular mechanisms underlying these effects involve increased myosin production and preserved a shuttle for transcription factors such as Runx2 from cytoplasm to nucleolus which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence. 3) The effects of blueberry diet on preserving fidelity of osteoblast differentiation also overcome reduced osteoblast differentiation and activity due to OVX-induced degradation of collagen matrix. Bone quality was compared among casein control diet sham operated, casein diet ovariectomized, long term BB diet ovariectomized, and short term BB diet ovariectomized female rats

ORGANISM(S): Rattus norvegicus

SUBMITTER: Kartik Shankar

PROVIDER: E-GEOD-30081 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description: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 17Î²-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a control diet with or without E2 (0.1, 1, 10 Âµg/kg/d), or SPI-containing diet with or without E2 (10 Âµg/kg/d) for 14 days beginning on postnatal day 20. In long bones from SPI-fed rats, only cancellous bone mineral density (BMD) was increased (p<0.05), while cortical BMD was decreased accompanied by lower bone strength compared to control casein-fed rats (p<0.05). In sharp contrast, 10 Âµg/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 sclerostin 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 suggest 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. The study was designed to compare expression of bone development associated genes between soy protein isolate fed and estrogen treated pre pubertal female rats. Therefore, total RNA was isolated from bone from rats fed with control casein diet, SPI diet, 17 beta estrodial treated and SPI diet plus 17 beta estrodial.

Project description:Gene expression along the crypt-villus (C-V) axis was analyzed using cryostat sectioning to isolate fractions representing the crypts (bottom) and villus tops (top). These fractions were used for analyzing gene expression in iron replete Wistar rats (++), iron deficient Wistar rats (low iron), and in iron deficient Wistar rats fed iron for 3 and 6 days (iron-fed). Differences were observed between the crypts and villus tops in the expression of genes associated with Wnt and BNP signaling, cell proliferation and apoptosis, lipid and iron transport and metabolism. Gene expression in villus crypts and tops was also compared between Wistar and Belgrade rats (bb) and Belgrade rats fed iron (iron-fed) particularly as related to iron absorption and metabolism to define the affects of the mutation in DMT1 in the Belgrade rat on the expression of genes related to iron absorption and metabolism and the response to iron feeding. Keywords: iron stress response A colony of Wistar strain rats (++) and Belgrade (bb) rats on a Wistar background maintained in our animal quarters was used for this study. Twelve one-month old ++ rats were separated into 3 groups of four rats each. Group 1 rats (samples 1-8) were fed a normal diet and served as control animals. Group 2 (samples 9-16) and Group 3 rats (samples 17-22) were fed a low iron diet and bled 2-3 ml every three days for 4 weeks and served as iron deficient rats (low-iron). Group 3 rats, of which one rat died during anesthesia while undergoing phlebotomy, were fed iron supplementation in drinking water (50 ÂµM Ferric ammonium citrate) for the three days before sacrifice (iron-fed). Rats were fasted overnight, killed by injection of pentobarbital sodium and a 1-cm duodenal segment 1 cm distal from the pylorus was cryostat sectioned at the right angle to the crypt-villus axis and the sections representing the top one-third of villus (top) and the bottom one-third of the villus were pooled for RNA isolation. For the study of Belgrade rats, eleven bb rats were divided into 3 groups with the 4 rats in Group 1 (samples 23-30) maintained on a normal diet, the 4 rats in Group 2 (samples 31-38) fed iron for 3 days prior to sacrifice, and the 3 rats in Group 3 (samples 39-44) fed iron for 6 days prior to sacrifice. All procedures for the bb rats were the same as described above for the ++ rats. An additional ++ rat (samples 45-46) was similarly analyzed in a separate experiment.

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Blueberry Diets during Early Development Only Is Sufficient to Prevent Senescence of Osteoblasts and Bone Loss in Adulthood

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