|Zhang, Jian -|
|Lazarenko, Oxana -|
|Kang, Jie -|
|Blackburn, Michael -|
|Ronis, Martin -|
|Chen, Jinran -|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 18, 2013
Publication Date: August 6, 2013
Citation: Zhang, J., Lazarenko, O.P., Kang, J., Blackburn, M.L., Ronis, M.J., Badger, T.M., Chen, J. 2013. Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of rankl in stromal cells. PLoS One. 8(8): e70438. Interpretive Summary: In our previous study, we have shown that 10% blueberry diet had significant effects on promoting bone growth. In the current study, we studied effects of different percentages of blueberry diet on bone growth. Experimental rats were fed 1%, 3%, or 5% blueberry die for one month. After blueberry diets, we found that rat bone mineral density and content were proportionally increased with blueberry supplementation from 1% to 5%. On the other hand, these three different blueberry supplementations did not have an effect on rat weight gain, total food intake, and total body fat. Even a diet supplemented with as low as 1% blueberry significantly increased bone strength over that of control diet rats. We suggest that phenolic acids derived from blueberry diet are the most important compounds to have positive effects on bone.
Technical Abstract: Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is as yet unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and also examined osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-kappa B ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPAR gamma which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes, and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.