Int. J. Mol. Sci. 2014, 15(7), 13010-13029; doi:10.3390/ijms150713010
Article

Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells

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Received: 16 June 2014; in revised form: 2 July 2014 / Accepted: 10 July 2014 / Published: 22 July 2014
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway.
Keywords: arginine; osteoblastogenesis; adipogenesis; NFATc/Wnt signaling pathway; mesenchymal stem cells
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MDPI and ACS Style

Huh, J.-E.; Choi, J.-Y.; Shin, Y.-O.; Park, D.-S.; Kang, J.W.; Nam, D.; Choi, D.-Y.; Lee, J.-D. Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells. Int. J. Mol. Sci. 2014, 15, 13010-13029.

AMA Style

Huh J-E, Choi J-Y, Shin Y-O, Park D-S, Kang JW, Nam D, Choi D-Y, Lee J-D. Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells. International Journal of Molecular Sciences. 2014; 15(7):13010-13029.

Chicago/Turabian Style

Huh, Jeong-Eun; Choi, Jun-Young; Shin, Ye-Ok; Park, Dong-Suk; Kang, Jung W.; Nam, Dongwoo; Choi, Do-Young; Lee, Jae-Dong. 2014. "Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells." Int. J. Mol. Sci. 15, no. 7: 13010-13029.


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