Cited by 122Bone Metabolism and DiseasesBone and Dental Protein StudiesCell Adhesion Molecules Research

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CYR61 Regulates BMP-2-dependent Osteoblast Differentiation through the αvβ3 Integrin/Integrin-linked Kinase/ERK Pathway

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Su, Jen-Liang, Chiou, Jean, Tang, Chih-Hsin, Zhao, Ming, Tsai, Chun-Hao, Chen, Pai-Sheng, Chang, Yi-Wen, Chien, Ming-Hsien, Peng, Chu-Ying, Hsiao, Michael, Kuo, Ming-Liang, Yen, Men-Luh·2010·Journal of Biological Chemistry

DOI 10.1074/jbc.m109.087122PMC PMC2951207

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Abstract

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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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: Chiou, Jean
Tang, Chih-Hsin
Zhao, Ming
Tsai, Chun-Hao
Chen, Pai-Sheng
Chien, Ming-Hsien
Hsiao, Michael
Kuo, Ming-Liang
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2010-10
Volume: 285
Issue: 41
Pages: 31325-31336
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m109.087122
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 3664 d)
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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CYR61 Regulates BMP-2-dependent Osteoblast Differentiation through the αvβ3 Integrin/Integrin-linked Kinase/ERK Pathway

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