ArticlePflugers Archiv : European journal of physiology2019
Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.
Article in Pflugers Archiv : European journal of physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Roles of Wnt/β-Catenin Signaling in Osteoporosis, Disease Pathogenesis, and Natural Compound Intervention.Biomolecules & therapeutics · 2026Review
- Parathyroid Hormone as a Modulator of Skeletal Muscle: Insights into Bone-Muscle and Nerve-Muscle Interactions.International journal of molecular sciences · 2025Review
- Research progress of connexins in epileptogensis.Acta epileptologica · 2025Review
- Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Bone-muscle crosstalk under physiological and pathological conditions.Cellular and molecular life sciences : CMLS · 2024Review
- Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis.Stem cell research & therapy · 2022Article
- Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading.eLife · 2022Article
- An Analysis Regarding the Association Between Connexins and Colorectal Cancer (CRC) Tumor Microenvironment.Journal of inflammation research · 2022Article
- Dysregulation of lncRNA-CCRR contributes to brain metastasis of breast cancer by intercellular coupling via regulating connexin 43 expression.Journal of cellular and molecular medicine · 2021Article
- Astragaloside‑IV modulates NGF‑induced osteoblast differentiation via the GSK3β/β‑catenin signalling pathway.Molecular medicine reports · 2021Article
- Reply "Comment on: Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration.International journal of molecular sciences · 2020Article
- p75NTRCell proliferation · 2020Article
- Hydroxyapatite Particle Density Regulates Osteoblastic Differentiation Through β-Catenin Translocation.Frontiers in bioengineering and biotechnology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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