Open Access

Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity

  • Authors:
    • Yan-Ling Feng
    • Xiao-Tong Jiang
    • Fang-Fang Ma
    • Jie Han
    • Xu-Lei Tang
  • View Affiliations

  • Published online on: October 23, 2017     https://doi.org/10.3892/ijmm.2017.3208
  • Pages:202-212
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resveratrol (3,5,4-trihydroxystilbene, RES), a natural antioxidant, prevents bone loss by attenuating damage caused by oxidative stress. Our previous research revealed that the forkhead box O1 (FoxO1)/β-catenin signaling pathway affected the proliferation and differentiation of osteoblasts through its regulation of redox balance, and RES regulated the expression of FoxO1 to control white adipose tissue and then ameliorate an overweight condition. Based on previous research, we hypothesized that RES regulates FoxO1 transcriptional activity through the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway to achieve an antioxidative effect on osteoporosis and then we confirmed this hypothesis in the present study. An ovariectomized (OVX) rat model of osteoporosis and a H2O2‑induced oxidative cell injury model in RAW 264.7 cells were established to explore the underlying molecular mechanisms of how RES confers an antioxidant effect and prevents bone loss. The obtained results demonstrated that RES strongly prevented bone loss induced by oxidative stress in vivo. More specifically, RES effectively decreased the receptor activator of nuclear factor-κB ligand (RANKL) together with the tartrate-resistant acid phosphatase‑5b (TRAP‑5b) level, but elevated the osteoproprotegrin (OPG) level and attenuated bone microarchitecture damage. Notably, RES, due to its antioxidant effect, suppressed RANKL production and then inhibited osteoclastogenesis in the OVX rats. In vitro, RES improved the oxidative stress status of cells and thus inhibited the mRNA expression of osteoclast-specific enzymes. These data indicate that RES has a significant bone protective effect by antagonizing oxidative stress to suppress osteoclast activity, function and formation both in vivo and in vitro. Moreover, at the molecular level, we confirmed, for the first time, that RES upregulated FoxO1 transcriptional activity by inhibiting the PI3K/AKT signaling pathway, and hence promoted resistance to oxidative damage and restrained osteoclastogenesis. Inhibition of the PI3K/AKT signaling pathway may be induced by RANKL. FoxO1 is a major action target of RES to confer anti-osteoporosis function, and whose effect stems from its power to improve redox balance.

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January 2018
Volume 41 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Feng, Y., Jiang, X., Ma, F., Han, J., & Tang, X. (2018). Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity. International Journal of Molecular Medicine, 41, 202-212. https://doi.org/10.3892/ijmm.2017.3208
MLA
Feng, Y., Jiang, X., Ma, F., Han, J., Tang, X."Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity". International Journal of Molecular Medicine 41.1 (2018): 202-212.
Chicago
Feng, Y., Jiang, X., Ma, F., Han, J., Tang, X."Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity". International Journal of Molecular Medicine 41, no. 1 (2018): 202-212. https://doi.org/10.3892/ijmm.2017.3208