|Chen, Jin-Ran -|
|Lazarenko, Oxana -|
|Wu, Xianli -|
|Kang, Jie -|
|Shankar, Kartik -|
|Blackburn, Michael -|
|Ronis, Martin -|
Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 5, 2010
Publication Date: November 15, 2010
Citation: Chen, J., Lazarenko, O.P., Wu, X., Kang, J., Shankar, K., Blackburn, M.L., Badger, T.M., Ronis, M.J. 2010. Dietary induced serum phenolic acids promote bone growth via p38 MAPK / Beta-Catenin Canonical Wnt signaling. Journal of Bone and Mineral Research. 25(11):2399-2411. Interpretive Summary: In early life, eating appropriate nutrition is one of the critical factors that influences bone development. We studied the effects of dietary blueberry supplementation on bone growth in weanling rats. Weanling male and female rats were fed AIN-93G semi-purified diets, supplemented with 10% whole blueberry powder for 14 and 30 d beginning on postnatal day 21. Specialized CT scan of long bones, showed dramatic increases in bone quality in both male and female rats consumed blueberry diets, compared with animals with control diets. Increased bone quality with blueberry diet was associated with an increasing of bone forming cells called osteoblasts. Increased bone forming cell osteoblasts, was further associated with enhanced differentiation of stem cells into mature osteoblasts. The potent osteoblast differentiation gene called Wnt was significantly activated by eating blueberry diet. We characterized phenolic acid in animals serum with blueberry diet, and we found 6 free forms (not bonded to other proteins) of phenolic acids synergistically stimulated bone cell differentiation. These results indicate significant stimulation of bone growth and osteoblast differentiation, associated with blueberry consumption in early development as a result of the actions of phenolic acid metabolites of blueberry polyphenols.
Technical Abstract: Diet and nutritional status are critical factors that influences bone development. In this report, we demonstrate that a mixture of phenolic acids found in the serum of young rats fed blueberries (BB), significantly stimulated osteoblast differentiation, resulting in significantly increased bone mass. Greater bone formation in BB-fed animals was associated with increases in osteoblast progenitors and osteoblast differentiation, and reduced osteoclastogenesis. Blockade of p38 phosphorylation, eliminated effects of BB on activation of Wnt signaling in pre-osteoblasts. Knocking down beta-catenin expression also blocked the ability of serum from BB diet-fed rats to stimulate osteoblast differentiation in vitro. Based on our in vivo and in vitro data, we propose that the underlying mechanisms of these powerful bone promoting effects, occur through beta-catenin activation and the nuclear accumulation and transactivation, of TCF/LEF gene transcription in bone and in osteoblasts. These results, indicate stimulation of molecular events leading to osteoblast differentiation triggered by P38 MAPK/beta-catenin canonical Wnt signaling, results in significant increases in bone growth in young rats consuming BB-supplemented diets. LC/MS characterization of the serum after BB feeding revealed a mixture of simple phenolic acids, which may provide basis for developing a new treatment to increase peak bone mass and delay degenerative bone disorders such as osteoporosis.