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Icariin Stimulates Differentiation and Suppresses Adipocytic Transdifferentiation of Primary Osteoblasts Through Estrogen Receptor-Mediated Pathway

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Abstract

Icariin, the main constituent of Herba Epimedii, appears to be a promising alternative to classic drugs used to treat osteoporosis. However, the detailed molecular mechanisms of its action and the role of icariin in the cross-talk between osteoblasts and adipocytes remain unclear. The present study was designed to investigate the gene expression profile of primary osteoblasts in the presence of icariin, and the effects of icariin on the differentiation and adipogenic transdifferentiation of osteoblasts. Cellular and molecular markers expressed during osteoblastic differentiation were assessed by cytochemical analysis, real-time quantitative PCR, Western blotting, and cDNA microarray analysis. Results indicated that icariin up-regulated the expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (Bmp2), and collagen type 1 (Col1) genes, and down-regulated the expression of the peroxisome proliferator-activated receptor γ (Pparg) and CCAAT/enhancer-binding protein β (Cebpb) genes. These effects were blocked by ICI 182,780, suggesting that icariin may be acting via the estrogen receptor (ER). Results also demonstrated that the ratio of osteoprotegerin (Opg)/receptor activator of nuclear factor kappa B ligand (Rankl) expression was up-regulated following treatment with icariin. In total, osteoblastic gene expression profile analysis suggested that 33 genes were affected by icariin; these could be sub-divided into nine functional categories. It appears that icariin could stimulate the differentiation and mineralization of osteoblasts, regulate the differentiation of osteoclasts, and inhibit the adipogenic transdifferentiation of osteoblasts, therefore increasing the number of osteoblasts undergoing differentiation to mature osteoblasts, via an ER-mediated pathway. In summary, icariin may exhibit beneficial effects on bone health, especially for patients with osteoporosis and obesity.

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Acknowledgments

This research was funded by the National Natural Science Foundation of China (No. 81402933, 81503465), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [(2014)-1685], the Natural Science Foundation of Guangdong Province (No. 2014A030313539, 2015A030310263), the Project for the Development of Social Science Research of Dongguan (No. 2013108101054), the Medical Scientific Research Foundation of Guangdong Province (B2014302, A2015347), 2014 Project of Teaching Quality and Teaching Reform of Undergraduate Course in Colleges and Universities in Guangdong Province, and the Doctor Scientific Start-up Fund Projects of Guangdong Medical College (B2012008).

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China

    Dawei Zhang, Zhenbin Jia & Liao Cui

  2. Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China

    Dawei Zhang & Liao Cui

  3. Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong

    Chichun Fong & Mengsu Yang

  4. Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Xinsheng Yao

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  1. Dawei Zhang
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Correspondence to Dawei Zhang or Mengsu Yang.

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Dawei Zhang, Chichun Fong, Zhenbin Jia, Liao Cui, Xinsheng Yao, and Mengsu Yang declare that they have no conflict of interest.

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All experiments were approved by the experimental animal ethics committee at Gugangdong Medical University and were conducted in accordance with the guidelines for the management and handling of experimental animals.

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Zhang, D., Fong, C., Jia, Z. et al. Icariin Stimulates Differentiation and Suppresses Adipocytic Transdifferentiation of Primary Osteoblasts Through Estrogen Receptor-Mediated Pathway. Calcif Tissue Int 99, 187–198 (2016). https://doi.org/10.1007/s00223-016-0138-2

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