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Updated: May 17, 2026

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Published on: October 27, 2020
CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling
Eriko Aoyama1, Satoshi Kubota, Masaharu Takigawa
1Biodental Research Center, Dental School, Okayama University, Okayama, Japan.
Abstract:
CCN2 plays a critical role in the development of mesenchymal tissues such as cartilage and bone, and the binding of CCN2 to various cytokines and receptors regulates their signaling.By screening a protein array, we found that CCN2 could bind to fibroblast growth factor receptors (FGFRs) 2 and 3, with a higher affinity toward FGFR2.We ascertained that FGFR2 bound to CCN2 and that the binding of FGFR2 to FGF2 and FGF4 was enhanced by CCN2.CCN2 and FGF2 had a collaborative effect on the phosphorylation of ERK and the differentiation of osteoblastic cells.The present results indicate the biological significance of the binding of CCN2 to FGFR2 in bone metabolism.
Insights
Cellular communication protein CCN2 binds to fibroblast growth factor receptors (FGFRs), particularly FGFR2, influencing bone cell development and signaling pathways crucial for bone metabolism.
Area of Science:
- Biochemistry
- Cell Biology
- Skeletal Biology
Background:
- Connective tissue growth factor (CCN2) is vital for mesenchymal tissue development, including cartilage and bone.
- CCN2 signaling is regulated by its interactions with cytokines and cellular receptors.
Purpose of the Study:
- To investigate the binding interaction between CCN2 and fibroblast growth factor receptors (FGFRs).
- To elucidate the functional consequences of CCN2-FGFR binding on bone cell biology and signaling.
Main Methods:
- Protein array screening to identify CCN2-binding partners.
- Co-immunoprecipitation assays to confirm CCN2-FGFR2 binding.
- Analysis of ERK phosphorylation and osteoblastic cell differentiation.
Main Results:
- CCN2 demonstrated binding affinity for FGFR2 and FGFR3, with a preference for FGFR2.
- CCN2 enhanced the binding of FGF2 and FGF4 to FGFR2.
- CCN2 and FGF2 synergistically promoted ERK phosphorylation and osteoblastic cell differentiation.
Conclusions:
- CCN2 directly binds to FGFR2, modulating its interaction with FGFs.
- The CCN2-FGFR2 interaction plays a significant role in regulating osteoblastic cell differentiation and bone metabolism.
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