ArticleCellular signalling2016
Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Role of soft tissue and bone interactions in the developmental integration and modularity of the skull in neural crest-specific gap junction alpha-1 knockout mice.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Loss of Function of the Retinoblastoma Gene Affects Gap Junctional Intercellular Communication and Cell Fate in Osteoblasts.Biology · 2024Article
- Gap junction-transported cAMP from the niche controls stem cell progeny differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Icariin Promotes Osteogenic Differentiation in a Cell Model with NF1 Gene Knockout by Activating the cAMP/PKA/CREB Pathway.Molecules (Basel, Switzerland) · 2023Article
- A two-dimensional finite element model of intercellular cAMP signaling through gap junction channels.Journal of biomechanics · 2023Article
- Basic Leucine Zipper Transcription Factors as Important Regulators of Leydig Cells' Functions.International journal of molecular sciences · 2022Review
- Taste Receptor Activation in Tracheal Brush Cells by Denatonium Modulates ENaC Channels via CaCells · 2022Article
- Update on the effects of microgravity on the musculoskeletal system.NPJ microgravity · 2021Review
- Gap Junction-Mediated Intercellular Communication of cAMP Prevents CDDP-Induced Ototoxicity via cAMP/PKA/CREB Pathway.International journal of molecular sciences · 2021Article
- Collagen synthesis and gap junctions: the highway for metastasis of ovarian cancer.Laboratory investigation; a journal of technical methods and pathology · 2021Article
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- Review
- Connexin expression decreases during adipogenic differentiation of human adipose-derived mesenchymal stem cells.Molecular biology reports · 2020Article
- Antagonistic Functions of Connexin 43 during the Development of Primary or Secondary Bone Tumors.Biomolecules · 2020Review
- Soluble silica stimulates osteogenic differentiation and gap junction communication in human dental follicle cells.Scientific reports · 2020Article
- The gap junction protein connexin 43 controls multiple aspects of cranial neural crest cell development.Journal of cell science · 2020Article
- Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.Pflugers Archiv : European journal of physiology · 2019Article
- Differential YAP nuclear signaling in healthy and dystrophic skeletal muscle.American journal of physiology. Cell physiology · 2019Article
- Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.Biochemical and biophysical research communications · 2019Article
- Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application.Journal of biomedical science · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Connexin43 (Cx43) containing gap junctions play an important role in bone homeostasis, yet little is known about the second messengers communicated by Cx43 among bone cells. Here, we used MC3T3-E1 pre-osteoblasts and UMR106 rat osteosarcoma cells to test the hypothesis that cAMP is a second messenger communicated by bone cells through Cx43 containing gap junctions in a manner that is sufficient to impact osteoblast function. Overexpression of Cx43 markedly enhanced the activity of a cAMP-response element driven transcriptional luciferase reporter (CRE-luc) and increased phospho-CREB and phospho-ERK1/2 levels following expression of a constitutively active Gsα or by treatment with prostaglandin E2 (PGE2), 3-Isobutyl-1-methyl xanthine (IBMX) or forskolin. The Cx43-dependent potentiation of signaling in PGE2 treated cells was not accompanied by a further increase in cAMP levels, suggesting that the cAMP was shared between cells rather than Cx43 enhancing cAMP production. To support this, we developed a novel assay in which one set of cells expressing constitutively active Gsα (donor cells) were co-cultured with a second set of cells expressing a CRE-luc reporter (acceptor cells). Using this assay, activation of a CRE-luc reporter in the acceptor cells was both Cx43- and cell contact-dependent, indicating communication of cAMP among cells. Finally, we showed that Cx43 increased the cAMP-dependent mRNA expression of receptor activator of nuclear factor kappa B ligand (RANKL) and enhanced the repression of the sclerostin mRNA, implying a potential mechanism for the modulation of tissue remodeling. In total, these data demonstrate that Cx43 can communicate cAMP between cells and, more importantly, that the communicated cAMP is sufficient to impact signal transduction cascades and the expression of key bone effector molecules between interconnected cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.