CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth

Sehee Choi, Hyun Yi Kim, Pu Hyeon Cha, Seol Hwa Seo, Chulho Lee, Yejoo Choi, Wookjin Shin, Yunseok Heo, Gyoonhee Han, Weon Tae Lee, Kang-Yell Choi

Research output: Contribution to journalArticle

Abstract

Longitudinal bone growth ceases with growth plate senescence during puberty. However, the molecular mechanisms of this phenomenon are largely unexplored. Here, we examined Wnt-responsive genes before and after growth plate senescence and found that CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt/β-catenin pathway, was gradually elevated with reduction of Wnt/β-catenin signaling during senescent changes of rodent growth plate. Cxxc5 2 / 2 mice demonstrated delayed growth plate senescence and tibial elongation. As CXXC5 functions by interacting with dishevelled (DVL), we sought to identify small molecules capable of disrupting this interaction. In vitro screening assay monitoring CXXC5–DVL interaction revealed that several indirubin analogs were effective antagonists of this interaction. A functionally improved indirubin derivative, KY19382, elongated tibial length through delayed senescence and further activation of the growth plate in adolescent mice. Collectively, our findings reveal an important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity.

Original languageEnglish
Article numbere201800254
JournalLife Science Alliance
Volume2
Issue number2
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

growth plate
Growth Plate
Bone Development
senescence
Fingers
bone
Bone
bones
protein
Catenins
Proteins
proteins
Wnt Signaling Pathway
mice
puberty
Puberty
antagonists
Rodentia
rodents
chemical derivatives

All Science Journal Classification (ASJC) codes

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

Cite this

Choi, Sehee ; Kim, Hyun Yi ; Cha, Pu Hyeon ; Seo, Seol Hwa ; Lee, Chulho ; Choi, Yejoo ; Shin, Wookjin ; Heo, Yunseok ; Han, Gyoonhee ; Lee, Weon Tae ; Choi, Kang-Yell. / CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth. In: Life Science Alliance. 2019 ; Vol. 2, No. 2.
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CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth. / Choi, Sehee; Kim, Hyun Yi; Cha, Pu Hyeon; Seo, Seol Hwa; Lee, Chulho; Choi, Yejoo; Shin, Wookjin; Heo, Yunseok; Han, Gyoonhee; Lee, Weon Tae; Choi, Kang-Yell.

In: Life Science Alliance, Vol. 2, No. 2, e201800254, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Choi, Yejoo

AU - Shin, Wookjin

AU - Heo, Yunseok

AU - Han, Gyoonhee

AU - Lee, Weon Tae

AU - Choi, Kang-Yell

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