CYR61 regulates BMP-2-dependent osteoblast differentiation through the αvβ3 integrin/integrin-linked kinase/ERK pathway

Jen Liang Su, Jean Chiou, Chih Hsin Tang, Ming Zhao, Chun Hao Tsai, Pai Sheng Chen, Yi Wen Chang, Ming Hsien Chien, Chu Ying Peng, Michael Hsiao, Ming Liang Kuo, Men Luh Yenk

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99 Citations (Scopus)


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 αvβ3 is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that integrin-linked kinase, which is downstream of the αvβ3 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-2mRNAand protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the αvβ3 integrin/integrin-linked kinase/ERK signaling pathway.

Original languageEnglish
Pages (from-to)31325-31336
Number of pages12
JournalJournal of Biological Chemistry
Issue number41
Publication statusPublished - Oct 8 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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