Connexin43 enhances Wnt and PGE2-dependent activation of ß-catenin in osteoblasts.
Pflugers Arch
; 471(9): 1235-1243, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31240382
ABSTRACT
Connexin43 is an important modulator of many signaling pathways in bone. ß-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 ß-catenin activity have been reported. Here, we examined how connexin43 influenced both Wnt-dependent and Wnt-independent activation of ß-catenin in osteoblasts in vitro. Our data show that loss of connexin43 in primary osteoblasts or connexin43 overexpression in UMR106 cells regulated active ß-catenin and phospho-Akt levels, with loss of connexin43 inhibiting and connexin43 overexpression increasing the levels of active ß-catenin and phospho-Akt. Increasing connexin43 expression synergistically enhanced Wnt3a-dependent activation of ß-catenin protein and ß-catenin transcriptional activity, as well as Wnt-independent activation of ß-catenin by prostaglandin E2 (PGE2). Finally, we show that the activation of ß-catenin by PGE2 required signaling through the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3 beta (GSK3ß) pathway, as the PI3K inhibitor, LY-294002, disrupted the synergy between connexin43 and PGE2. These data show that connexin43 regulates Akt and ß-catenin activity and synergistically enhances both Wnt-dependent and Wnt-independent ß-catenin signaling in osteoblasts.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoblastos
/
Dinoprostona
/
Conexina 43
/
Proteínas Wnt
/
Beta Catenina
Límite:
Animals
Idioma:
En
Revista:
Pflugers Arch
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos