CCN1/Cyr61 Is Regulated by the Canonical Wnt Signal and Plays an Important Role in Wnt3A-Induced Osteoblast Differentiation of Mesenchymal Stem Cells
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Marrow mesenchymal stem cells are pluripotent progenitors that can differentiate into bone, cartilage, muscle, and fat cells. Wnt signaling has been implicated in regulating osteogenic differentiation of mesenchymal stem cells. Here, we analyzed the gene expression profile of mesenchymal stem cells that were stimulated with Wnt3A. Among the 220 genes whose expression was significantly changed by 2.5-fold, we found that three members of the CCN family, CCN1/Cyr61, CCN2/connective tissue growth factor (CTGF), and CCN5/WISP2, were among the most significantly up-regulated genes. We further investigated the role of CCN1/Cyr61 in Wnt3A-regulated osteogenic differentiation. We confirmed that CCN1/Cyr61 was up-regulated at the early stage of Wnt3A stimulation. Chromatin immunoprecipitation analysis indicates that CCN1/Cyr61 is a direct target of canonical Wnt/beta-catenin signaling. RNA interference-mediated knockdown of CCN1/Cyr61 expression diminished Wnt3A-induced osteogenic differentiation. Furthermore, exogenously expressed CCN1/Cyr61 was shown to effectively promote mesenchymal stem cell migration. These findings suggest that tightly regulated CCN1/Cyr61 expression may play an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
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CCN1 stimulates osteoblast differentiation through an αvβ3/ILK-dependent pathway but inhibits osteoclastogenesis, suggesting it is a bifunctional regulator of bone remodeling that promotes bone formation and inhibits bone resorption.
“Moreover, CCN1 stimulates osteoblast differentiation through an αvβ3/ILK-dependent pathway but inhibits osteoclastogenesis, suggesting its role as a bifunctional regulator of bone remodeling that promotes bone formation but inhibits bone resorption [90–92].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [90]
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References 63 · Cited by 272
- Authors
- Si, W., Kang, Q., Luu, H. H., Park, J. K., Luo, Q., Song, W.-X., Jiang, W., Luo, X., Li, X., Yin, H., Montag, A. G., Haydon, R. C., & He, T.-C.
- Affiliations
- Army Medical University (CN)
- University of Chicago Medical Center (US)
- Molecular Oncology Laboratory, Department of Surgery, University of Chicago Medical Center
- University of Chicago (US)
- Corresponding author
- He, Tong-Chuan
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-04
- Volume
- 26
- Issue
- 8
- Pages
- 2955-2964
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1446962
- OpenAlex
- W2122364340
- Cited by
- 272
- References
- 63
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 12 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 18 · 2014: 16 · 2013: 27 · 2012: 20
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brinson Foundation
- University of Illinois at Chicago
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt3a, canonical Wnt/β-catenin pathway, osteogenic differentiation, mesenchymal stem cells, CCN family, connective tissue growth factor, WISP2, gene expression profiling, stem cell migration
- MeSH terms
- Adenoviridae, Alkaline Phosphatase, Cell Differentiation, Cell Line, Cell Movement, Gene Expression Regulation, Humans, Osteoblasts, Blotting, Western, Signal Transduction, Polymerase Chain Reaction, Immediate-Early Proteins, Gene Expression Profiling, RNA Interference, Intercellular Signaling Peptides and Proteins, Protein Array Analysis, HCT116 Cells, Chromatin Immunoprecipitation, Wnt Proteins, Cysteine-Rich Protein 61, Mesenchymal Stem Cells
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