title: Arsenic trioxide regulates adipogenic and osteogenic differentiation in bone marrow MSCs of aplastic anemia patients through BMP4 gene.
abstract: The typical pathological feature of aplastic anemia (AA) is the rise in the number of fat cells and the reduction of osteoblasts in bone marrow. However, both fat cells and osteobalsts in bone marrow are derived from the mesenchymal stem cells (MSCs). Generally, the adipogenic and osteogenic differentiation is a dynamic and balanceable process. The imbalance of the adipogenic and osteogenic differentiation may participate in the occurrence and progress of many diseases. Arsenic trioxide (ATO) could induce differentiation and apoptosis in tumor cells. In this study, Oil Red-O and Alizarin red were used to detect the adipogenic and osteogenic differentiation. The ability of adipogenic differentiation is much higher, whereas the osteogenic differentiation is much lower in the MSCs of AA patients compared with healthy controls. ATO inhibits adipogenic differentiation and promotes osteogenic differentiation in the MSC of AA patients. The expression of BMP4 is increased with ATO treatment. The ability of adipogenic differentiation is decreased, whereas the osteogenic differentiation is increased after transfection of BMP4 gene into the MSCs of AA patients. This study shows that ATO regulates the adipogenic and osteogenic differentiation balance of MSCs in AA, which provides a theoretical basis for the adjunctive therapy of ATO on AA. The BMP4 gene is involved in the ATO regulation of adipogenic and osteogenic differentiation balance, which provides a new target for the treatment of AA.
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Huan Chen
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Sheng Wei
authors.initials: SW
authors.lastname: Liu
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Xue Fei
authors.initials: XF
authors.lastname: Zhao
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Institute of Hematology and Oncology, the First Hospital of Harbin, Harbin 150010, China haerbinxys@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000328:Adult; D000741:Anemia, Aplastic / Q000473:pathology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D016922:Cellular Senescence; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010087:Oxides / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D010087:Oxides; D000077237:Arsenic Trioxide
keywords: BMP4; arsenic trioxide; differentiation; mesenchymal stem cells