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

Authors
 H-Y Kim  ;  J-Y Yoon  ;  J-H Yun  ;  K-W Cho  ;  S-H Lee  ;  Y-M Rhee  ;  H-S Jung  ;  H J Lim  ;  H Lee  ;  J Choi  ;  J-N Heo  ;  W Lee  ;  K T No  ;  D Min  ;  K-Y Choi 
Citation
 CELL DEATH AND DIFFERENTIATION, Vol.22(6) : 912-920, 2015 
Journal Title
CELL DEATH AND DIFFERENTIATION
ISSN
 1350-9047 
Issue Date
2015
MeSH
Animals ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cell Line ; Humans ; Mice ; Mice, Knockout ; Osteoblasts/cytology* ; Osteoblasts/metabolism* ; Receptors, CXCR5/genetics ; Receptors, CXCR5/metabolism* ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/physiology* ; beta Catenin/metabolism*
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.
Full Text
http://www.nature.com/cdd/journal/v22/n6/full/cdd2014238a.html
DOI
10.1038/cdd.2014.238
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Rhee, Yumie(이유미) ORCID logo https://orcid.org/0000-0003-4227-5638
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140161
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