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CYR61 Regulates BMP-2-dependent Osteoblast Differentiation through the αvβ3 Integrin/Integrin-linked Kinase/ERK Pathway
- Source :
- Journal of Biological Chemistry. 285:31325-31336
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
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.
- Subjects :
- Time Factors
MAP Kinase Signaling System
Bone Morphogenetic Protein 2
Protein Serine-Threonine Kinases
Biochemistry
Bone morphogenetic protein 2
Gene Expression Regulation, Enzymologic
Cell Line
Mice
Animals
Integrin-linked kinase
c-Raf
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Cell Proliferation
Integrin alphaVbeta3
Osteoblasts
Dose-Response Relationship, Drug
biology
Cell Differentiation
Cell Biology
BMPR2
Cell biology
Bone morphogenetic protein 7
Integrin alpha M
biology.protein
Cancer research
Integrin, beta 6
Cysteine-Rich Protein 61
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....ff1f39a1f3cdc55dd42ad15edf919f61