Open AccessConnexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts
Author(s) -
Aditi Gupta,
Saimai Chatree,
Atum M. Buo,
Megan C. Moorer,
Joseph P. Stains
Publication year - 2019
Publication title -
pflügers archiv für die gesamte physiologie des menschen und der tiere/pflügers archiv
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.428
H-Index - 129
eISSN - 0365-267X
pISSN - 0031-6768
DOI - 10.1007/s00424-019-02295-y
Subject(s) - wnt signaling pathway , microbiology and biotechnology , protein kinase b , gsk 3 , catenin , wnt3a , pi3k/akt/mtor pathway , beta catenin , chemistry , osteoblast , signal transduction , lrp5 , kinase , biology , in vitro , biochemistry
Connexin43 is an important modulator of many signaling pathways in bone. β-Catenin, a key regulator of the osteoblast differentiation and function, is among the pathways downstream of connexin43-dependent intercellular communication. There are striking overlaps between the functions of these two proteins in bone cells. However, differential effects of connexin43 on β-catenin activity have been reported. Here, we examined how connexin43 influenced both Wnt-dependent and Wnt-independent activation of β-catenin in osteoblasts in vitro. Our data show that loss of connexin43 in primary osteoblasts or connexin43 overexpression in UMR106 cells regulated active β-catenin and phospho-Akt levels, with loss of connexin43 inhibiting and connexin43 overexpression increasing the levels of active β-catenin and phospho-Akt. Increasing connexin43 expression synergistically enhanced Wnt3a-dependent activation of β-catenin protein and β-catenin transcriptional activity, as well as Wnt-independent activation of β-catenin by prostaglandin E2 (PGE2). Finally, we show that the activation of β-catenin by PGE2 required signaling through the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 beta (GSK3β) pathway, as the PI3K inhibitor, LY-294002, disrupted the synergy between connexin43 and PGE2. These data show that connexin43 regulates Akt and β-catenin activity and synergistically enhances both Wnt-dependent and Wnt-independent β-catenin signaling in osteoblasts.