title: Neobavaisoflavone stimulates osteogenesis via p38-mediated up-regulation of transcription factors and osteoid genes expression in MC3T3-E1 cells.
abstract: Neobavaisoflavone (NBIF) is an isoflavone isolated from Psoralea corylifolia L, a plant claimed to have osteogenic activity and used to treat bone fractures, osteomalacia and osteoporosis. The present results showed that NBIF concentration-dependently promoted osteogenesis in MC3T3-E1cells, demonstrated by notable enhancement of alkaline phosphatase (ALP) activity, increase of bone-specific matrix proteins expression including type I collagen (Col-I), osteocalcin (OCN) and bone sialoprotein (BSP), and formation of bone nodules. However, cell proliferation in the presence of NBIF was not affected. Results also demonstrated that NBIF up-regulated the expression of runt-related transcription factor 2 (Runx2) and Osterix (Osx), the bone-specific transcription factors participating in regulation of bone marker genes expression. Application of p38 inhibitor SB203580 repressed not only NBIF-induced activation of ALP, the expression of Col-I, OCN and BSP, but also the matrix proteins mineralization. Western blot analysis further revealed that NBIF increased the phosphorylated level of p38 concentration-dependently. Additionally, inhibition of p38 abolished the stimulatory effect of NBIF on the expression of Runx2 and Osx. Taken together, the osteogenic activity of NBIF might probably act through activation of p38-dependent signaling pathway to up-regulate the mRNA levels of Runx2 and Osx then stimulate bone matrix proteins expression. The beneficial effect of NBIF on mineralization demonstrated that NBIF represented as an active component existed in P. corylifolia and might be a potential anabolic agent to treat bone loss-associated diseases.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan.
authors.forename: Ming-Jaw
authors.initials: MJ
authors.lastname: Don
authors.forename: Lie-Chwen
authors.initials: LC
authors.lastname: Lin
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Chiou
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects* / Q000201:enzymology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004341:Drug Evaluation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D007887:Fabaceae; D015870:Gene Expression / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology; D029907:Psoralea / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D007529:Isoflavones; D010936:Plant Extracts; D010938:Plant Oils; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C550193:babchi oil; C549830:neobavaisoflavone; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase