title: Gremlin2 Suppression Increases the BMP-2-Induced Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells Via the BMP-2/Smad/Runx2 Signaling Pathway.
abstract: Osteoblasts are essential for maintaining skeletal architecture and modulating bone microenvironment homeostasis. From numerous associated investigations, the BMP-2 pathway has been well-defined as a vital positive modulator of bone homeostasis. Gremlin2 (Grem2) is a bone morphogenetic protein (BMP) antagonists. However, the effect of Grem2 on the BMP-2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs) remains ambiguous. This study aimed to analyze the procedure in vitro and in vivo. The differentiation of hBMSCs was assessed by determining the expression levels of several osteoblastic genes, as well as the enzymatic activity and calcification of alkaline phosphatase. We found that Grem2 expression was upregulated by BMP-2 within the range of 0-1 μg/mL, and significant increases were evident at 48, 72, and 96 h after BMP-2 treatment. Si-Grem2 increased the BMP-2-induced osteogenic differentiation of hBMSCs, whereas overexpression of Grem2 had the opposite trend. The result was confirmed using a defective femur model. We also discovered that the BMP-2/Smad/Runx2 pathway played an important role in the process. This study showed that si-Grem2 increased the BMP-2-induced osteogenic differentiation of hBMSCs via the BMP-2/Smad/Runx2 pathway. J. Cell. Biochem. 118: 286-297, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chuan-Dong
authors.initials: CD
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zuo
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: De
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Xu-Yi
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Wei-Jia
authors.initials: WJ
authors.lastname: Feng
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Zhuo-Kai
authors.initials: ZK
authors.lastname: Li
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Hu
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.|Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D016207:Cytokines; C495107:GREM2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C493709:RUNX2 protein, human; D051785:Smad Proteins
keywords: BMP-2; GREM2; OSTEOGENIC DIFFERENTIATION; RUNX2; SMAD; hBMSCs