| RRC ID |
57745
|
| 著者 |
Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, Shin W, Heo Y, Han G, Lee W, Choi KY.
|
| タイトル |
CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth.
|
| ジャーナル |
Life Sci Alliance
|
| 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-/-
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.
|
| 巻・号 |
2(2)
|
| 公開日 |
2019-4-1
|
| DOI |
10.26508/lsa.201800254
|
| PII |
2/2/e201800254
|
| PMID |
30971423
|
| PMC |
PMC6458850
|
| MeSH |
Animals
Bone Development / physiology*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Dishevelled Proteins / metabolism
Growth Plate / metabolism*
HEK293 Cells
Humans
Indoles / pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction / drug effects
Transcription Factors / genetics
Transcription Factors / metabolism*
Transfection
Wnt Signaling Pathway
beta Catenin / metabolism
|
| IF |
2.622
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
