Departmental Papers (Dental)
Bone Morphogenetic Protein-2 Promotes Osteosarcoma Growth by Promoting Epithelial-Mesenchymal Transition (EMT) Through the Wnt/b-Catenin Signaling Pathway
Date of this Version
Journal of Orthopaedic Research
The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/β-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while β-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3β were also significantly upregulated indicating that the Wnt/β-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/β-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638–1648, 2019. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
bone morphogenetic protein-2, epithelial-mesenchymal transition, osteosarcoma, Wnt/β-catenin, Animals, Bone Morphogenetic Protein 2, Bone Neoplasms, Cell Line, Tumor, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Humans, Male, Mice, Mice, SCID, Osteosarcoma, Wnt Signaling Pathway, axin2 protein, beta catenin, bone morphogenetic protein 2, cyclin D1, dickkopf 1 protein, glycogen synthase kinase 3beta, Myc protein, protein, unclassified drug, Wnt protein, Wnt3a protein, bone morphogenetic protein 2, animal experiment, animal model, animal tissue, Article, cancer growth, cell invasion, cell migration, cell motility, cell proliferation, down regulation, epithelial mesenchymal transition, human, human cell, in vitro study, in vivo study, male, mouse, nonhuman, nude mouse, osteosarcoma, osteosarcoma cell, priority journal, signal transduction, tumor model, tumor volume, tumor weight, upregulation, animal, bone tumor, cell motion, drug effect, epithelial mesenchymal transition, osteosarcoma, SCID mouse, tumor cell line, Wnt signaling
Tian, H., Zhou, T., Chen, H., Li, C., Jiang, Z., Lao, L., Kahn, S. A., Duarte, M. E., Zhao, J., Daubs, M. D., Buser, Z., Brochmann, E. J., Wang, J. C., & Murray, S. S. (2019). Bone Morphogenetic Protein-2 Promotes Osteosarcoma Growth by Promoting Epithelial-Mesenchymal Transition (EMT) Through the Wnt/b-Catenin Signaling Pathway. Journal of Orthopaedic Research, 37 (7), 1638-1648. http://dx.doi.org/10.1002/jor.24244
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.