KMID : 0624620120450090509
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BMB Reports 2012 Volume.45 No. 9 p.509 ~ p.514
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Biphasic effects of TGF¥â1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells
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Li Rui-Dong
Deng Zhong-Liang Hu Ning Liang Xi Liu Bo Luo Jinyong Chen Liang Yin Liangjun Luo Xiaoji Shui Wei He Tong-Chuan Huang Wei
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Abstract
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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¥â1 duringosteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGF¥â1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of TGF¥â1 inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of TGF¥â1 potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGF¥â1 decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that TGF¥â1 inhibits C3H10T1/2 proliferation inBMP9-induced osteogenesis and restricts the cells in G(0)/G(1) phase. Our findings strongly suggest that TGF¥â1 may exert a biphasic effect on BMP9-induced osteogenic differentiation ofmesenchymal stem cells.
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KEYWORD
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BMP9, Mesenchymal stem cells, Osteogenic differentiation, Osteoprogenitors, TGF¥â1
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