Publication: Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts
Issued Date
2019-09-01
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ISSN
14322013
00316768
00316768
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2-s2.0-85067999840
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Mahidol University
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SCOPUS
Bibliographic Citation
Pflugers Archiv European Journal of Physiology. Vol.471, No.9 (2019), 1235-1243
Suggested Citation
Aditi Gupta, Saimai Chatree, Atum M. Buo, Megan C. Moorer, Joseph P. Stains Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts. Pflugers Archiv European Journal of Physiology. Vol.471, No.9 (2019), 1235-1243. doi:10.1007/s00424-019-02295-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50087
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Title
Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts
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Abstract
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. 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.