title: Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma             cell growth and migration through downregulation of the PI3K/AKT pathway.
abstract: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily             of signaling molecules and have previously been shown to be associated with the             biological behavior of osteosarcoma. However, to date the effects and molecular             mechanisms of BMP-9 on osteosarcoma progression are unknown. We performed real-time             PCR and western blot analysis to characterize the endogenous expression of BMP-9             in osteosarcoma cell lines. We used a recombinant adenovirus expressing BMP-9             (adBMP-9) to infect osteosarcoma cell lines with relatively low endogenous BMP-9             expression to determine the functional relevance of BMP-9 overexpression to osteosarcoma             cell growth and migration in vitro and in vivo, and further investigated the expression             levels of Ki-67, matrix metallopeptidase-9 (MMP-9), phosphoinositide 3-kinase             p85α (PI3Kp85α) and phosphorylated AKT (p-AKT). As a result, osteosarcoma cell             proliferation and migration were significantly diminished by adBMP-9, indicated             by MTT and wound-healing assays, and cell apoptosis was markedly induced, indicated             by Hoechst 33342/PI assay and Annexin V-FITC apoptosis detection. When BMP-9 expression             was enhanced, the expression of PI3Kp85α, p-AKT, Ki-67 and MMP-9 was downregulated             in osteosarcoma cells. In addition, the tumor volumes in MG-63 and HOS subcutaneous             nude mouse models treated with adBMP-9 were significantly smaller compared to             those of the ad-GFP group. These results suggested that the enhanced expression             of BMP-9 in osteosarcoma cells by adBMP-9 exerted inhibitory effects on growth             and migration of osteosarcoma cells possibly via blockade of the PI3K/AKT signaling             pathway.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Yang
authors.forename: Shengdan
authors.initials: S
authors.lastname: Jiang
authors.forename: Binbin
authors.initials: B
authors.lastname: Ni
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Leisheng
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D055427:Growth Differentiation Factor 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D055427:Growth Differentiation Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt