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

被引：78

作者：

Kim, H-Y ^{[1
,2
]}

Yoon, Y. ^{[1
,2
]}

Yun, J-H ^{[3
]}

Cho, K-W ^{[4
]}

Lee, S-H ^{[1
,2
]}

Rhee, Y-M ^{[5
]}

Jung, H-S ^{[4
]}

Lim, H. J. ^{[6
]}

Lee, H. ^{[6
]}

Choi, J. ^{[7
]}

Heo, J-N ^{[6
]}

Lee, W. ^{[3
]}

No, K. T. ^{[2
,7
]}

Min, D. ^{[1
,8
]}

Choi, K-Y ^{[1
,2
]}

机构：

[1] Yonsei Univ, Translat Res Ctr Prot Funct Control, Seoul 120749, South Korea

[2] Yonsei Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul 120749, South Korea

[3] Yonsei Univ, Dept Biochem, Coll Life Sci & Biotechnol, Seoul 120749, South Korea

[4] Yonsei Univ, Dept Oral Biol, Coll Dent, Res Ctr Orofacial Hard Tissue Regenerat, Seoul 120749, South Korea

[5] Yonsei Univ, Dept Internal Med, Coll Med, Seoul 120749, South Korea

[6] Korea Res Inst Chem Technol, Taejon 305606, South Korea

[7] Yonsei Univ, Bioinformat & Mol Design Res Ctr, Seoul 120749, South Korea

[8] Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, Busan, South Korea

来源：

CELL DEATH AND DIFFERENTIATION | 2015年 / 22卷 / 06期

关键词：

BONE; TARGET; IDAX;

D O I：

10.1038/cdd.2014.238

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The positive roles of the Wnt/beta-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/beta-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/beta-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/beta-catenin pathway and osteoblast differentiation, and accelerated thickness growth of ex vivo-cultured calvariae. Overall, CXXC5 is a negative-feedback regulator induced by Wnt/beta-catenin signaling that inhibits osteoblast differentiation and bone formation via interaction with Dvl.

引用

页码：912 / 920

页数：9

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