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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

  • Li, Rui-Dong (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Deng, Zhong-Liang (Department of Orthopaedic Surgery, the Second Affiliated Hospital, Chongqing Medical University) ;
  • Hu, Ning (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Liang, Xi (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Liu, Bo (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Luo, Jin-Yong (Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center) ;
  • Chen, Liang (Department of Orthopaedic Surgery, the Second Affiliated Hospital, Chongqing Medical University) ;
  • Yin, Liangjun (Department of Orthopaedic Surgery, the Second Affiliated Hospital, Chongqing Medical University) ;
  • Luo, Xiaoji (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Shui, Wei (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • He, Tong-Chuan (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University) ;
  • Huang, Wei (Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University)
  • Received : 2012.03.12
  • Accepted : 2012.06.05
  • Published : 2012.09.30
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Abstract

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with $TGF{\beta}1$ during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rh$TGF{\beta}1$ synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of $TGF{\beta}1$ inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of $TGF{\beta}1$ potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of $TGF{\beta}1$ decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that $TGF{\beta}1$ inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in $G_0/G_1$ phase. Our findings strongly suggest that $TGF{\beta}1$ may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Keywords

References

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