title: Bone morphogenetic protein 9 regulates tumor growth of osteosarcoma cells through the Wnt/β-catenin pathway.
abstract: Bone morphogenetic protein 9 (BMP9) is a member of the transforming growth factor-β (TGF-β) family, which has been shown to regulate the progression of several tumors. Recent studies indicated that BMP9 affects osteosarcoma (OS) processes, but its specific roles and molecular mechanisms have yet to be fully elucidated. The human OS cell lines 143B and MG63 were used for the present study. We found that BMP9 overexpression suppressed the growth of OS cells, whereas inhibition of BMP9 reversed this effect. Our results also showed that BMP9 overexpression induced G0/G1 phase arrest and apoptosis in OS cells. We further investigated the possible molecular mechanisms mediating the biological role of BMP9. We observed that BMP9 overexpression reduced β-catenin mRNA and protein levels, and also downregulated its downstream proteins c-Myc and osteoprotegerin (OPG) and inhibited the phosphorylation levels of GSK-3β (Ser 9) in OS cells, whereas inhibition of BMP9 reversed these effects. Moreover, the suppressive effects of BMP9 overexpression on OS cells was reversed by exogenous β-catenin expression, but augmented by β-catenin silencing. In conclusion, our results revealed that BMP9 can regulate tumor growth of OS cells through the Wnt/β-catenin pathway. Therefore, BMP9 may be a new therapeutic target in OS.
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Zilan
authors: Z
authors: Lv
authors: Department of Gastroenterology, The Third People's Hospital of Chongqing, Chongqing 400014, P.R. China.
authors: Chuan
authors: C
authors: Wang
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Taixian
authors: T
authors: Yuan
authors: Department of Clinical Laboratory, The Fourth Hospital of Xi'an, Xi'an, Shaanxi 710004, P.R. China.
authors: Yuehong
authors: Y
authors: Liu
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Tao
authors: T
authors: Song
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Yueliang
authors: Y
authors: Liu
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Chu
authors: C
authors: Chen
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Min
authors: M
authors: Yang
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Zuchuan
authors: Z
authors: Tang
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Qiong
authors: Q
authors: Shi
authors: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors: Yaguang
authors: Y
authors: Weng
mesh_terms: D000199:Actins / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000276:immunology / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D053244:Osteoprotegerin / Q000096:biosynthesis; D012516:Osteosarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000276:immunology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D000199:Actins; D000906:Antibodies; D017077:Culture Media, Conditioned; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; C489427:MYC protein, human; D053244:Osteoprotegerin; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3