title: Du-Huo-Ji-Sheng-Tang and its active component Ligusticum chuanxiong promote osteogenic differentiation and decrease the aging process of human mesenchymal stem cells.
abstract: BACKGROUND
  Postmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking.
  
  
  OBJECTIVE
  This study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs).
  
  
  METHODS
  hMSCs were used as in vitro model and osteogenesis was induced by administration of either osteogenesis inducing medium (OIM) or dexamethasone-depleted OIM (DDOIM) for 1-week or 2 weeks and the results were evaluated by measuring the formation of mineralization nodules. The effects of the compound recipe DHJST and its active component L. chuanxiong on hMSCs osteogenesis-related gene expression was determined by real-time PCR that targeted bone morphogenetic protein-2 (BMP2), RUNX2, ALP, COL-1, osteopontin (OPN), and osteocalcin (OCN). Antibodies against BMP-related signaling pathway proteins, such as BMP-2, ERK, SMAD 1/5/8, and RUNX2, were also detected at the protein level by Western blotting. Finally, the cumulative growth curve and senescence of the hMSCs were evaluated in order to assess the aging process.
  
  
  RESULTS
  L. chuanxiong increased osteogenic activity in hMSCs and up-regulated BMP-2 and RUNX2 gene expression via the activation of SMAD 1/5/8 and ERK signaling. Furthermore DHJST also showed a trend towards promoting the same effects in the same system. In the absence of dexamethasone, DHJST did activate SMAD 1/5/8 and ERK signaling and hence increased RUNX2 protein expression in hMSCs. In addition, both DHJST and L. chuanxiong delayed the hMSCs aging process by decreasing cell senescence.
  
  
  CONCLUSIONS
  We concluded that DHJST and its active component L. chuanxiong are able to promote osteogenic activity and decrease hMSCs senescence as cells age.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: jywang7@vghtpe.gov.tw.
authors.forename: Jir-You
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC.
authors.forename: Che-Sheng
authors.initials: CS
authors.lastname: Wen
authors.affiliation: Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Chen
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of General Surgery, Departml;ent of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC; Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jen-Hwey
authors.initials: JH
authors.lastname: Chiu
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D030004:Ligusticum; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D004365:Drugs, Chinese Herbal; C493709:RUNX2 protein, human
keywords: Herbal medicine; Ligusticum chuanxiong; Mesenchymal stem cell; Osteogenesis; Senescence