The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ
Open accessAbstract
Mesenchymal precursor cells have the potential to differentiate into several cell types, including adipocytes and osteoblasts. Activation of Wnt/beta-catenin signaling shifts mesenchymal cell fate toward osteoblastogenesis at the expense of adipogenesis; however, molecular mechanisms by which Wnt signaling alters mesenchymal cell fate have not been fully investigated. Our prior work indicates that multipotent precursors express adipogenic and osteoblastogenic transcription factors at physiological levels and that ectopic expression of Wnt10b in bipotential ST2 cells suppresses expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) and increases expression of Runx2, Dlx5, and osterix. Here, we demonstrate that transient activation of Wnt/beta-catenin signaling rapidly suppresses C/EBPalpha and PPARgamma, followed by activation of osteoblastogenic transcription factors. Enforced expression of C/EBPalpha or PPARgamma partially rescues lipid accumulation and decreases mineralization in ST2 cells expressing Wnt10b, suggesting that suppression of C/EBPalpha and PPARgamma is required for Wnt/beta-catenin to alter cell fate. Furthermore, knocking down expression of C/EBPalpha, PPARgamma, or both greatly reduces adipogenic potential and causes spontaneous osteoblastogenesis in ST2 cells and mouse embryonic fibroblasts, suggesting that Wnt signaling alters the fate of mesenchymal precursor cells primarily by suppressing C/EBPalpha and PPARgamma.
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Cites
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Regulation of bone mass by Wnt signaling
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Cited by
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Cristancho, A. G., & Lazar, M. A. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3198 · Cited by 1,382
Skeletal remodeling in health and disease
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Growth Hormone, Insulin-Like Growth Factors, and the Skeleton
Giustina, A., Mazziotti, G., & Canalis, E. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0036 · Cited by 914
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
Osteoblast and osteocyte: Games without frontiers
Capulli, M., Paone, R., & Rucci, N. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.05.003 · Cited by 413
Metadata
- Authors
- Kang, S., Bennett, C. N., Gerin, I., Rapp, L. A., Hankenson, K. D., & MacDougald, O. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 282
- Issue
- 19
- Pages
- 14515-14524
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2010221831
- Cited by
- 401
- References
- 11
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ. https://app.cochat.ai/papers/10.1074/jbc.m700030200
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- Kang, S., Bennett, C. N., Gerin, I., Rapp, L. A., Hankenson, K. D., & MacDougald, O. A. (2007). Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m700030200
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