title: The role of COX-2 in mediating the effect of PTEN on BMP9 induced osteogenic differentiation in mouse embryonic fibroblasts.
abstract: Mouse embryonic fibroblasts (MEFs) are multi-potent progenitor cells (MPCs), can differentiate into different lineages, such as osteogenic, and adipogenic. PTEN, a tumor suppressor, may be involved in regulating bone development through interacting with COX-2. BMP9, the most potent osteogenic BMPs, can up-regulate COX-2 in MPCs. Whether PTEN is involved in BMP9 induced osteogenic differentiation in MPCs remains unknown. The goal of this investigation is to identify the effect of PTEN on BMP9-induced osteogenic differentiation in MPCs and dissect the possible mechanism underlay this. We found that BMP9 down-regulates PTEN, and PTEN inhibitor (VO) effectively increases different osteogenic markers induced by BMP9 in MEFs. Exogenous expression of PTEN inhibits BMP9 induced ectopic bone formation apparently. Mechanistically, we found that VO can enhance BMP9 induced BMPs/Smads signaling prominently without no substantial effects on cell cycle. Further analysis indicates that VO can promote BMP9-induced expression of COX-2 in MEFs, which can be eliminated by PI3K inhibitor. Additionally, COX-2 knockdown abolishes the effect of VO on BMP9-induced ALP activities in MEFs. Our findings suggest that PTEN plays an important role in regulating BMP9 induced osteogenic differentiation in MPCs, which may be mediated by PTEN/PI3K/Akt signaling to modulate the expression of COX-2.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Shuang-Xue
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Qiu-Xiang
authors.initials: QX
authors.lastname: Wu
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Pi
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zou
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Ying
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Jun-Qing
authors.initials: JQ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Sun
authors.affiliation: Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China; Department of Orthopedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People's Republic of China. Electronic address: 894704897@qq.com.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D055427:Growth Differentiation Factor 2 / Q000378:metabolism*; D051379:Mice; D010012:Osteogenesis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: BMP9; COX-2; MEFs; Osteogenic differentiation; PI3K/Akt; PTEN