|CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)|
|LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)|
|ZHANG, JIAN - Arkansas Children'S Nutrition Research Center (ACNC)|
|BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)|
|RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/29/2013
Publication Date: 5/1/2014
Citation: Chen, J., Lazarenko, O.P., Zhang, J., Blackburn, M.L., Ronis, M.J., Badger, T.M. 2014. Diet derived phenolic acids regulate osteoblast and adipocyte lineage commitment and differentiation in young mice. Journal of Bone and Mineral Research. 29(5):1043-1053.
Interpretive Summary: We previously published that a blueberry (BB)-containing diet significantly stimulated bone growth in young male and female rats. Digestion of BB produces metabolites such as polyphenols and phenolic acids (PAs). Thus, after a BB-containing meal the concentrations of PAs in rat blood were significantly higher. We speculated that this increased blood PA concentration was one of reasons for elevated bone growth in rats consuming BB. In the current study, we treated bone-forming cells (called osteoblasts) with a solution containing the same concentrations of PAs found in the blood of BB-consuming rats and found significantly greater numbers of osteoblasts compared to cells treated without PAs. In addition, we injected mice with the PA-containing solution once a day for 15 days. The PA-treated mice had stronger bones compared to those mice treated with just saline injections. We further found that PA treatment activated a protein call G protein coupled receptor 109A, a protein involved in bone development. Based upon these data, we conclude that PAs are capable of altering the bone cell differentiation program which is important for normal bone development and this merits additional investigation as potential dietary therapeutic alternatives to drugs for degenerative bone disorders.
Technical Abstract: A blueberry (BB) supplemented diet previously has been shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and they were found in the serum of rats fed BB-containing diet. We conducted in vitro studies with PAs and demonstrated stimulation of osteoblast differentiation and proliferation. On the other hand, adipogenesis was inhibited. To more fully understand the mechanistic actions of PAs on bone formation, we administered hippuric acid, one of the major metabolites found in animal circulation after BB consumption, to prepubertal female mice for two weeks. We found that hippuric acid was able to stimulate bone-forming gene expression but suppress PPAR' expression leading to increased bone mass dose-dependently. Cellular signaling studies further suggested that the skeletal effects of PAs appeared to be mediated through activation of G protein coupled receptor 109A and down-stream p38 MAP kinase and osterix. In conclusion, PAs are capable of altering the mesenchymal stem cell differentiation program and merit investigation as potential dietary therapeutic alternatives to drugs for degenerative bone disorders.