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

H. Y. Kim, J. Y. Yoon, J. H. Yun, K. W. Cho, S. H. Lee, Yumie Rhee, Hansung Jung, H. J. Lim, H. Lee, J. Choi, J. N. Heo, Weon Tae Lee, Kyoung Tai No, D. Min, Kang-Yell Choi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)912-920
Number of pages9
JournalCell Death and Differentiation
Volume22
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

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Catenins
Wnt Signaling Pathway
Osteoblasts
Fingers
Proteins
Osteogenesis
Bone Density
Skull
Maintenance
Peptides
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Kim, H. Y. ; Yoon, J. Y. ; Yun, J. H. ; Cho, K. W. ; Lee, S. H. ; Rhee, Yumie ; Jung, Hansung ; Lim, H. J. ; Lee, H. ; Choi, J. ; Heo, J. N. ; Lee, Weon Tae ; No, Kyoung Tai ; Min, D. ; Choi, Kang-Yell. / CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation. In: Cell Death and Differentiation. 2015 ; Vol. 22, No. 6. pp. 912-920.
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CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation. / Kim, H. Y.; Yoon, J. Y.; Yun, J. H.; Cho, K. W.; Lee, S. H.; Rhee, Yumie; Jung, Hansung; Lim, H. J.; Lee, H.; Choi, J.; Heo, J. N.; Lee, Weon Tae; No, Kyoung Tai; Min, D.; Choi, Kang-Yell.

In: Cell Death and Differentiation, Vol. 22, No. 6, 01.06.2015, p. 912-920.

Research output: Contribution to journalArticle

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T1 - CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation

AU - Kim, H. Y.

AU - Yoon, J. Y.

AU - Yun, J. H.

AU - Cho, K. W.

AU - Lee, S. H.

AU - Rhee, Yumie

AU - Jung, Hansung

AU - Lim, H. J.

AU - Lee, H.

AU - Choi, J.

AU - Heo, J. N.

AU - Lee, Weon Tae

AU - No, Kyoung Tai

AU - Min, D.

AU - Choi, Kang-Yell

PY - 2015/6/1

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N2 - 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.

AB - 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.

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