Diet-Derived Phenolic Acids Regulate Osteoblast and Adipocyte Lineage Commitment and Differentiation in Young Mice

Authors

  • Jin-Ran Chen,

    Corresponding author
    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    • Address correspondence to: Jin-Ran Chen, PhD, Arkansas Children's Nutrition Center, Slot 512-20B, 15 Children's Way, Little Rock, AR 72202, USA. E-mail: chenjinran@uams.edu

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  • Oxana P Lazarenko,

    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Departments of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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  • Jian Zhang,

    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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  • Michael L Blackburn,

    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Departments of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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  • Martin JJ Ronis,

    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    3. Departments of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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  • Thomas M Badger

    1. Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    2. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    3. Departments of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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  • For a Commentary on this article, please see Chen and Anderson (J Bone Miner Res. 2014;29: 1041–1042. DOI: 10.1002/jbmr.2234).

ABSTRACT

A blueberry (BB)-supplemented diet has been previously 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 2 weeks. We found that hippuric acid was able to stimulate bone-forming gene expression but suppress PPARγ 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 downstream 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. © 2014 American Society for Bone and Mineral Research.

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