Open Access

Simvastatin inhibits the adipogenesis of bone marrow‑derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling

  • Authors:
    • Yao Guo
    • Jianzhong Huo
    • Dou Wu
    • Haihu Hao
    • Xinghua Ji
    • Enzhe Zhao
    • Boyuan Nie
    • Qiang Liu
  • View Affiliations

  • Published online on: May 18, 2020     https://doi.org/10.3892/ijmm.2020.4606
  • Pages: 751-761
  • Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Simvastatin is effective in the treatment of osteoporosis, partly through the inhibition of the adipogenesis of bone‑marrow derived mesenchymal stem cells (BMSCs). The present study focused on the mechanisms responsible for the inhibitory effects of simvastatin on adipogenesis and examined the effects of simvastatin on the expression of peroxisome proliferator‑activated receptor γ (PPARγ), chemerin, chemokine‑like receptor 1 (CMKLR1), G protein‑coupled receptor 1 (GPR1) and the adipocyte marker gene, adiponectin. BMSCs were isolated from 4‑week‑old female Sprague‑Dawley (SD) rats, and adipogenesis was measured by the absorbance values at 490 nm of Oil Red O dye. The expression of each gene was evaluated by western blot analysis or reverse transcription‑quantitative PCR (RT‑qPCR). The expression of chemerin increased during adipogenesis, while CMKLR1 exhibited a trend towards a decreased expression. On days 7 and 14, the simvastatin‑treated cells exhibited a downregulated expression of chemerin, whereas the upregulated expression of its receptor, CMKLR1 was observed. The results also revealed that CMKLR1 is required for adipogenesis and the simvastatin‑mediated inhibitory effect on adipogenesis. Simvastatin regulated adipogenesis by negatively modulating chemerin‑CMKLR1 signaling. Importantly, simvastatin stimulation inhibited the upregulation of PPARγ and PPARγ‑mediated chemerin expression to prevent adipogenesis. Treatment with the PPARγ agonist, rosiglitazone, partially reversed the negative regulatory effects of simvastatin. On the whole, the findings of the present study demonstrate that simvastatin inhibits the adipogenesis of BMSCs through the downregulation of PPARγ and subsequently prevents the PPARγ‑mediated induction of chemerin/CMKLR1 signaling.
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August-2020
Volume 46 Issue 2

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

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APA
Guo, Y., Huo, J., Wu, D., Hao, H., Ji, X., Zhao, E. ... Liu, Q. (2020). Simvastatin inhibits the adipogenesis of bone marrow‑derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling. International Journal of Molecular Medicine, 46, 751-761. https://doi.org/10.3892/ijmm.2020.4606
MLA
Guo, Y., Huo, J., Wu, D., Hao, H., Ji, X., Zhao, E., Nie, B., Liu, Q."Simvastatin inhibits the adipogenesis of bone marrow‑derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling". International Journal of Molecular Medicine 46.2 (2020): 751-761.
Chicago
Guo, Y., Huo, J., Wu, D., Hao, H., Ji, X., Zhao, E., Nie, B., Liu, Q."Simvastatin inhibits the adipogenesis of bone marrow‑derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling". International Journal of Molecular Medicine 46, no. 2 (2020): 751-761. https://doi.org/10.3892/ijmm.2020.4606