title: Baicalin, a flavone, induces the differentiation of cultured osteoblasts: an action via the Wnt/beta-catenin signaling pathway.
abstract: Flavonoids, a group of natural compounds found in a variety of vegetables and herbal medicines, have been intensively reported on regarding their estrogen-like activities and particularly their ability to affect bone metabolism. Here, different subclasses of flavonoids were screened for their osteogenic properties by measuring alkaline phosphatase activity in cultured rat osteoblasts. The flavone baicalin derived mainly from the roots of Scutellaria baicalensis showed the strongest induction of alkaline phosphatase activity. In cultured osteoblasts, application of baicalin increased significantly the osteoblastic mineralization and the levels of mRNAs encoding the bone differentiation markers, including osteonectin, osteocalcin, and collagen type 1α1. Interestingly, the osteogenic effect of baicalin was not mediated by its estrogenic activity. In contrast, baicalin promoted osteoblastic differentiation via the activation of the Wnt/β-catenin signaling pathway; the activation resulted in the phosphorylation of glycogen synthase kinase 3β and, subsequently, induced the nuclear accumulation of the β-catenin, leading to the transcription activation of Wnt-targeted genes for osteogenesis. The baicalin-induced osteogenic effects were fully abolished by DKK-1, a blocker of Wnt/β-catenin receptor. Moreover, baicalin also enhanced the mRNA expression of osteoprotegerin, which could regulate indirectly the activation of osteoclasts. Taken together, our results suggested that baicalin could act via Wnt/β-catenin signaling to promote osteoblastic differentiation. The osteogenic flavonoids could be very useful in finding potential drugs, or food supplements, for treating post-menopausal osteoporosis.
authors.affiliation: Division of Life Science and Center for Chinese Medicine, Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong.
authors.forename: Ava J Y
authors.initials: AJ
authors.lastname: Guo
authors.forename: Roy C Y
authors.initials: RC
authors.lastname: Choi
authors.forename: Anna W H
authors.initials: AW
authors.lastname: Cheung
authors.forename: Vicky P
authors.initials: VP
authors.lastname: Chen
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Xu
authors.forename: Tina T X
authors.initials: TT
authors.lastname: Dong
authors.forename: Ji J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Karl W K
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C531384:Dkk1 protein, rat; D004791:Enzyme Inhibitors; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; C038044:baicalin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3