title: Icariin promotes osteogenic differentiation of rat bone marrow stromal cells by activating the ERα-Wnt/β-catenin signaling pathway.
abstract: Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis. rBMSCs were cultured in osteogenic induction medium and treated with icariin or together with ICI 182780 or DKK1, the effects on the expression of osteogenic genes and Wnt/β-catenin signaling were detected. Results indicated that icariin (0.1μM) markedly enhanced the proliferation of rBMSCs and alkaline phosphatase (ALP) activity. Additionally, icariin (0.1μM) significantly up-regulated the expression of osteogenic genes (Runx2, osteopotin, DLX5, osteocalcin, collagen type I, and ERα) and Wnt signal members (β-catenin, Lef1, TCF7, c-jun, c-myc, and cyclin D). Furthermore, icariin stimulated the activation of β-catenin as evidenced by increased total β-catenin protein and nuclear translocation. These osteogenesis-potentiating effects of icariin were blocked by ICI 182780 or DKK1. Taken together, these results suggest that the osteogenic effects of icariin on rBMSCs involves the ERα-Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Baiyun District, Guangzhou, Guangdong 510405, China; Key Laboratory of Orthopaedics & Traumatology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: QiuShi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Anatomy, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Orthopaedics & Traumatology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: GuoJu
authors.initials: G
authors.lastname: Hong
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Baiyun District, Guangzhou, Guangdong 510405, China.
authors.forename: ZhenQiu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Rehabilitation, General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China.
authors.forename: WeiMin
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Baiyun District, Guangzhou, Guangdong 510405, China; Key Laboratory of Orthopaedics & Traumatology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: hw13802516062@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Key Laboratory of Orthopaedics & Traumatology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China. Electronic address: chenmeihuionly@163.com.
authors.forename: Mei Hui
authors.initials: MH
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D047628:Estrogen Receptor alpha; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; D000077267:Fulvestrant; D004958:Estradiol; C056599:icariin
keywords: Bone marrow stromal cells; Icariin; Osteogenic differentiation; Wnt/β-catenin signaling