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

Guo,Yao; Huo,Jianzhong; Wu,Dou; Hao,Haihu; Ji,Xinghua; Zhao,Enzhe; Nie,Boyuan; Liu,Qiang

doi:10.3892/ijmm.2020.4606

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
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Affiliations: Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China, Department of Orthopaedics, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
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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