Location: Arkansas Children's Nutrition CenterTitle: P38 MAPK / beta-catenin canonical wnt signaling mediated bone formation effects of blueberries Author
Submitted to: American Society for Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 7/9/2009
Publication Date: 9/17/2009
Citation: Chen, J., Lazarenko, O., Wu, X., Shankar, K., Blackburn, M., Badger, T.M., Ronis, M.J. 2009. P38 MAPK / beta-catenin canonical wnt signaling mediated bone formation effects of blueberries. American Society for Bone and Mineral Research. J Bone Miner Res 24 (Suppl 1). Available at [http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=31715c3e-5624-4b5e-a0e1-3e9575e786a5]. Interpretive Summary:
Technical Abstract: 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. Using peripheral quantitative CT scan of tibia, we demonstrate that, in both sexes, bone mass including bone mineral density and content were significantly increased in blueberry supplemented rats compared to control AIN-93G fed animals. Body weight gains were not affected. Ex-vivo osteoblastogenesis and osteoclastogenesis assays, along with histomorphometric studies, revealed that increased bone formation in blueberry-fed animals was associated with an increase in osteoblast differentiation and numbers of osteoblast progenitors while reducing osteoclastogenesis. Rats fed blueberry diets evidenced greater beta-catenin activation in bone. This was recapitulated ex vivo where serum from blueberry-fed animals stimulated beta-catenin activation, nuclear accumulation, and transactivated TCF/LEF gene transcription in cultured osteoblasts. Further, blueberry feeding and serum from rats fed blueberry diets activated p38 MAPK and Runx2, but not Msx2, both in vivo and in pre-osteoblasts in vitro. Blocking phosphorylation of p38 eliminated the effect of blueberry serum on activation of beta-catenin signaling in pre-osteoblasts. Finally, polyphenol-derived phenolic acids in serum from blueberry diet animals were quantified on LC/MS and their concentrations were compared to those from control diet animals. Six phenolic acids in their free forms were found in high concentrations in serum from blueberry diet animals compared to controls. When an artificial mixture of these phenolic acids at the same concentration found in serum of blueberry-fed rats in vivo was incubated with ST-2 and C2C12 osteoblast-precursor cell lines in culture, significant increases in osteoblast differentiation as measured by expression of alkaline phosphate, osteocalcin and Runx2 mRNA were observed. 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.