title: Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells.
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 TGFβ1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFβ1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of TGFβ1 inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of TGFβ1 potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGFβ1 decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that TGFβ1 inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in G(0)/G(1) phase. Our findings strongly suggest that TGFβ1 may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells.
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Li
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.forename: Xi
authors.initials: X
authors.lastname: Liang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Liangjun
authors.initials: L
authors.lastname: Yin
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Shui
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D055427:Growth Differentiation Factor 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D055427:Growth Differentiation Factor 2; D011994:Recombinant Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D053495:Osteopontin