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CYR61 Regulates BMP-2-dependent Osteoblast Differentiation through the αvβ3 Integrin/Integrin-linked Kinase/ERK Pathway
Open accessAbstract
Osteoporosis is one of the most common bone pathologies. A number of novel molecules have been reported to increase bone formation including cysteine-rich protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear. It is known that bone morphogenetic proteins (BMPs), especially BMP-2, are crucial regulators of osteogenesis. However, the interaction between CYR61 and BMP-2 is unclear. We found that CYR61 significantly increases proliferation and osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in a time- and dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic differentiation are significantly decreased by knockdown of BMP-2 expression or inhibition of BMP-2 activity. In this study we found integrin α(v)β(3) is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that integrin-linked kinase, which is downstream of the α(v)β(3) receptor, is involved in CYR61-induced BMP-2 expression and subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken together, our results show that CYR61 up-regulates BMP-2 mRNA and protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the α(v)β(3) integrin/integrin-linked kinase/ERK signaling pathway.
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“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 [92]
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Metadata
- Authors
- Su, J.-L., Chiou, J., Tang, C.-H., Zhao, M., Tsai, C.-H., Chen, P.-S., Chang, Y.-W., Chien, M.-H., Peng, C.-Y., Hsiao, M., Kuo, M.-L., & Yen, M.-L.
- Affiliations
- Asia University (TW)
- China Medical University (TW)
- University of Missouri–Kansas City (US)
- China Medical University Hospital (TW)
- National Taiwan University (TW)
- Genomics Research Center, Academia Sinica (TW)
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 285
- Issue
- 41
- Pages
- 31325-31336
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2951207
- OpenAlex
- W2006409326
- Cited by
- 121
- References
- 69
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 10 · 2019: 15 · 2018: 3 · 2017: 2 · 2016: 10 · 2015: 10 · 2014: 14 · 2013: 10 · 2012: 13
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Academia Sinica
- National Health Research Institutes
- China Medical University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CYR61, BMP-2, osteogenic differentiation, osteoblast proliferation, integrin αvβ3, integrin-linked kinase, ERK signaling, bone morphogenetic proteins, bone formation, osteoporosis, MC3T3-E1 cells
- MeSH terms
- Scaffold Protein ILK, Animals, Cell Differentiation, Cell Line, Dose-Response Relationship, Drug, Osteoblasts, Time Factors, Gene Expression Regulation, Enzymologic, Protein Serine-Threonine Kinases, MAP Kinase Signaling System, Integrin alphaVbeta3, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Mice, Bone Morphogenetic Protein 2, Cysteine-Rich Protein 61
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