Journal
CALCIFIED TISSUE INTERNATIONAL
Volume 99, Issue 2, Pages 187-198Publisher
SPRINGER
DOI: 10.1007/s00223-016-0138-2
Keywords
Primary osteoblast; Icariin; Estrogen receptor; Adipogenesis; Gene expression profile
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Funding
- National Natural Science Foundation of China [81402933, 81503465]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [(2014)-1685]
- Natural Science Foundation of Guangdong Province [2014A030313539, 2015A03031 0263]
- Project for the Development of Social Science Research of Dongguan [2013108101054]
- Medical Scientific Research Foundation of Guangdong Province [B2014302, A2015347]
- Project of Teaching Quality and Teaching Reform of Undergraduate Course in Colleges and Universities in Guangdong Province
- Doctor Scientific Start-up Fund Projects of Guangdong Medical College [B2012008]
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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 gamma (Pparg) and CCAAT/enhancer-binding protein beta (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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