title: MiR-101 Targets the EZH2/Wnt/β-Catenin the Pathway to Promote the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
abstract: Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs. MiR-101 depletion suppressed osteogenic differentiation, whereas the overexpression of miR-101 was sufficient to promote this process. We further demonstrated that enhancer of zeste homolog 2 (EZH2) was a target gene of miR-101. EZH2 overexpression and depletion reversed the promoting or suppressing effect of osteogenic differentiation of hBMSCs, respectively, caused by miR-101. In addition, we showed that miR-101 overexpression promoted the expression of Wnt genes, resulting in the activation of the Wnt/β-catenin signaling pathway by targeting EZH2, while the activity of β-catenin and the Wnt/β-catenin signaling pathway was inhibited by ICG-001, a β-Catenin inhibitor, which reversed the promoting effect of miR-101. Finally, miR-101 also promotes in vivo bone formation by hBMSCs. Collectively, these data suggest that miR-101 is induced by osteogenic stimuli and promotes osteogenic differentiation at least partly by targeting the EZH2/Wnt/β-Catenin signaling pathway.
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Yake
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Orthopedic Surgery,University of Virginia, 400 Ray C. Hunt Drive, Charlottesville, VA 22903, USA.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville VA 22908, USA.
authors.forename: Fujun
authors.initials: F
authors.lastname: Qin
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Haisong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics,Changhai Hospital, The Second Military Medical University of China, 168 Changhai Road, Shanghai 200433, P.R. China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Departmentof Orthopaedics, Changzheng Hospital, The Second Military Medical University of China, 415 Fengyang Road, Shanghai 200003, P.R. China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Guo
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D010012:Osteogenesis; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein