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Bergapten promotes bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo.

Abstract
Many recent studies have suggested that bergapten (BP), a class of native compound with numerous biological activities such as anti-resorptive properties, may exert protective effects against postmenopausal bone loss. However, it remains unknown whether BP regulates or improves the osteogenic function of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In our study, BMSCs were cultured in osteogenic induction medium with the addition of BP for 2 weeks and an ovariectomized mouse model of osteoporosis was used to investigate the anti-resorptive effect of BP by gavage administration for 3 months. The concentrations of BP used were 0.1, 1, and 10 μmol/L in vitro and the gavage dose was 20 mg/kg/d. The result of our study indicated that BP promotes the expression of alkaline phosphatase (ALP) by BMSCs in vitro in a dose-dependent manner, as revealed by ALP staining. Runt-related transcription factor 2 and osteocalcin were up-regulated both in vitro and vivo, while osterix and collagen Iα1, assessed by immunofluorescence and immunohistochemistry, were correspondingly raised in the presence of BP in BMSCs in vitro. In addition, a protective effect of BP against ovariectomy-induced bone loss was found by distal femur micro-CT scanning, with improvements of bone metabolism parameters such as bone mineral density, trabecular number, and trabecular separation. Furthermore, WNT/β-catenin signaling was activated in the presence of BP in BMSCs in osteogenic culture. Finally, BP promoted differentiation of BMSCs into osteoblasts by up-regulation of the WNT/β-catenin pathway.
AuthorsJi-jie Xiao, Wen-ji Zhao, Xin-tao Zhang, Wen-long Zhao, Xiao-xia Wang, Shu-hui Yin, Fang Jiang, Yin-xia Zhao, Fang-ni Chen, Shao-lin Li
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 409 Issue 1-2 Pg. 113-22 (Nov 2015) ISSN: 1573-4919 [Electronic] Netherlands
PMID26188800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • Photosensitizing Agents
  • Runx2 protein, mouse
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Osteocalcin
  • 5-Methoxypsoralen
  • Alkaline Phosphatase
  • Methoxsalen
Topics
  • 5-Methoxypsoralen
  • Alkaline Phosphatase (biosynthesis)
  • Animals
  • Bone Marrow Cells (cytology)
  • Cell Differentiation (drug effects)
  • Cells, Cultured
  • Collagen Type I (biosynthesis)
  • Core Binding Factor Alpha 1 Subunit (biosynthesis)
  • Female
  • Mesenchymal Stem Cells (cytology)
  • Methoxsalen (analogs & derivatives, pharmacology)
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts (cytology)
  • Osteocalcin (biosynthesis)
  • Osteogenesis (drug effects)
  • Osteoporosis (pathology)
  • Photosensitizing Agents (pharmacology)
  • Sp7 Transcription Factor
  • Transcription Factors (biosynthesis)
  • Wnt Proteins (metabolism)
  • Wnt Signaling Pathway (drug effects)
  • beta Catenin (metabolism)

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