title: Icariin Stimulates Differentiation and Suppresses Adipocytic Transdifferentiation of Primary Osteoblasts Through Estrogen Receptor-Mediated Pathway.
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.
authors.affiliation: School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China. dwzhang@gdmu.edu.cn.|Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China. dwzhang@gdmu.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong.
authors.forename: Chichun
authors.initials: C
authors.lastname: Fong
authors.affiliation: School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Jia
authors.affiliation: School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People's Republic of China.|Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
authors.forename: Liao
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong. bhmyang@cityu.edu.hk.
authors.forename: Mengsu
authors.initials: M
authors.lastname: Yang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects
chemical_list: D005419:Flavonoids; D053245:RANK Ligand; D011960:Receptors, Estrogen; C056599:icariin
keywords: Adipogenesis; Estrogen receptor; Gene expression profile; Icariin; Primary osteoblast