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

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

SUBMITTER: Choi S 

PROVIDER: S-EPMC6458850 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature