Reference - Detail
| RRC ID | 57745 |
|---|---|
| Author | Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, Shin W, Heo Y, Han G, Lee W, Choi KY. |
| Title | CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth. |
| Journal | 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. |
| Volume | 2(2) |
| Published | 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 |
| Times Cited | 1 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |