Open AccessLRP 5 negatively regulates differentiation of monocytes through abrogation of Wnt signalling
Author(s) -
BorrellPagès Maria,
Romero July Carolina,
Badimon Lina
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12190
Subject(s) - lrp5 , wnt signaling pathway , microbiology and biotechnology , cellular differentiation , lrp6 , biology , gene silencing , effector , chemistry , signal transduction , gene , genetics
Molecular changes involved in cell differentiation are only partially known. Circulating inflammatory cells need to differentiate to perform specialized functions in target tissues. Here, we hypothesized that low‐density lipoprotein receptor–related protein 5 ( LRP 5) is involved, through its participation in the canonical Wnt/β‐catenin signalling, in the differentiation process of monocytic cells. To this aim, we characterized differentiation mechanisms of HL 60 cells and primary human monocytes. We show that silencing the LRP 5 gene increased differentiation of HL 60 cells and human monocytes, suggesting that LRP 5 signalling abrogates differentiation. We demonstrate that the mechanisms behind this blockade include sequestration of β‐catenin at the cellular membrane, inhibition of the Wnt signalling and increase of apoptosis. We further demonstrate the involvement of LRP 5 and the Wnt/β‐catenin signalling in the process because cellular differentiation can be rescued by the addition of downstream Wnt target genes to the monocytic cells.