Format

Send to

Choose Destination
Cell Death Differ. 2015 Jun;22(6):912-20. doi: 10.1038/cdd.2014.238. Epub 2015 Jan 30.

CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation.

Author information

1
1] Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea [2] Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
2
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
3
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
4
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
5
Korea Research Institute of Chemical Technology, Daejeon, Korea.
6
Bioinformatics and Molecular Design Research Center, Yonsei University, Seoul, Korea.
7
1] Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea [2] Bioinformatics and Molecular Design Research Center, Yonsei University, Seoul, Korea.
8
1] Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea [2] Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Korea.

Abstract

The positive roles of the Wnt/β-catenin pathway in osteoblast differentiation and bone mineral density (BMD) maintenance have been clearly demonstrated in both animal experiments and clinical investigations. CXXC finger protein 5 (CXXC5), a recently identified negative regulator of the Wnt/β-catenin pathway, showed altered cellular localization and function, which were dependent on the cell type in previous studies. However, the in vivo function of CXXC5 has not been clearly investigated yet. Here, we characterized CXXC5 as a negative regulator of osteoblast differentiation and bone formation. Deficiency of CXXC5 resulted in elevated BMD in mice without any severe gross developmental abnormalities. CXXC5 exerted a negative-feedback effect on the Wnt/β-catenin pathway via Wnt-dependent binding to Dishevelled (Dvl) during osteoblast differentiation. Suppression of the Dvl-CXXC5 interaction using a competitor peptide resulted in the activation of the Wnt/β-catenin pathway and osteoblast differentiation, and accelerated thickness growth of ex vivo-cultured calvariae. Overall, CXXC5 is a negative-feedback regulator induced by Wnt/β-catenin signaling that inhibits osteoblast differentiation and bone formation via interaction with Dvl.

PMID:
25633194
PMCID:
PMC4423189
DOI:
10.1038/cdd.2014.238
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center