The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Hypoxia Inhibits Osteogenesis in Human Mesenchymal Stem Cells through Direct Regulation of RUNX2 by TWIST
Open accessAbstract
BACKGROUND: Bone loss induced by hypoxia is associated with various pathophysiological conditions, however, little is known about the effects of hypoxia and related signaling pathways on osteoblast differentiation and bone formation. Because bone marrow-derived mesenchymal stem cells (MSCs) survive under hypoxic conditions and readily differentiate into osteoblasts by standard induction protocols, they are a good in vitro model to study the effects of hypoxia on osteoblast differentiation. METHODOLOGY/PRINCIPLE FINDINGS: Using human MSCs, we discovered TWIST, a downstream target of HIF-1α, was induced under hypoxia and acted as a transcription repressor of RUNX2 through binding to the E-box located on the promoter of type 1 RUNX2. Suppression of type 1 RUNX2 by TWIST under hypoxia further inhibited the expression of BMP2, type 2 RUNX2 and downstream targets of RUNX2 in MSCs. CONCLUSIONS/SIGNIFICANCE: Our findings point to the important role of hypoxia-mediated signalling in osteogenic differentiation in MSCs through direct regulation of RUNX2 by TWIST, and provide a method for modifying MSC osteogenesis upon application of these cells in fracture healing and bone reconstruction.
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Cites
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Direct regulation of TWIST by HIF-1α promotes metastasis
Yang, M.-H., Wu, M.-Z., Chiou, S.-H., Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., & Wu, K.-J. (2008) · Nature Cell Biology · doi:10.1038/ncb1691 · Cited by 1,345
Self-citationCanonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
Gaur, T., Lengner, C. J., Hovhannisyan, H., Bhat, R. A., Bodine, P. V. N., Komm, B. S., Javed, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500608200 · Cited by 1,170
Hiraga, T., Kizaka-Kondoh, S., Hirota, K., Hiraoka, M., & Yoneda, T. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2355 · Cited by 242
Cited by
Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?
Chen, Q., Shou, P., Zheng, C., Jiang, M., Cao, G., Yang, Q., Cao, J., Xie, N., Velletri, T., Zhang, X., et al. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.168 · Cited by 1,156
Key transcription factors in the differentiation of mesenchymal stem cells
Almalki, S. G., & Agrawal, D. K. (2016) · Differentiation · doi:10.1016/j.diff.2016.02.005 · Cited by 420
Sart, S., Tsai, A.-C., Li, Y., & Ma, T. (2014) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2013.0537 · Cited by 382
Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells
Qadir, A., Liang, S., Wu, Z., Chen, Z., Hu, L., & Qian, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21010349 · Cited by 268
Boyette, L. B., Creasey, O. A., Guzik, L., Lozito, T., & Tuan, R. S. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2013-0079 · Cited by 121
Metadata
- Authors
- Yang, D.-C., Yang, M.-H., Tsai, C.-C., Huang, T.-F., Chen, Y.-H., & Hung, S.-C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-09-09
- Volume
- 6
- Issue
- 9
- Pages
- e23965
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2048539785
- Cited by
- 181
- References
- 4
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yang, D.-C., Yang, M.-H., Tsai, C.-C., Huang, T.-F., Chen, Y.-H., & Hung, S.-C. (2011). Hypoxia Inhibits Osteogenesis in Human Mesenchymal Stem Cells through Direct Regulation of RUNX2 by TWIST. PLoS ONE. https://doi.org/10.1371/journal.pone.0023965
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