ArticleMolecular biology of the cell2009
Connexin43 potentiates osteoblast responsiveness to fibroblast growth factor 2 via a protein kinase C-delta/Runx2-dependent mechanism.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- Connexin 43 Hemichannels Regulate Osteoblast to Osteocyte Differentiation.Frontiers in cell and developmental biology · 2022Article
- Bone fracture healing: perspectives according to molecular basis.Journal of bone and mineral metabolism · 2021Review
- Relationship Between Hematoma Expansion Induced by Hypertension and Hyperglycemia and Blood-brain Barrier Disruption in Mice and Its Possible Mechanism: Role of Aquaporin-4 and Connexin43.Neuroscience bulletin · 2020Article
- Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.Biochemical and biophysical research communications · 2019Article
- Molecular signaling in bone cells: Regulation of cell differentiation and survival.Advances in protein chemistry and structural biology · 2019Review
- Joint diseases: from connexins to gap junctions.Nature reviews. Rheumatology · 2017Review
- Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal Development, and Osteoblast and Osteoclast Function.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation.Journal of cell science · 2017Article
- Connexin43 and the Intercellular Signaling Network Regulating Skeletal Remodeling.Current osteoporosis reports · 2017Review
- Deficiency of the intermediate filament synemin reduces bone mass in vivo.American journal of physiology. Cell physiology · 2016Article
- Inhibition of connexin 43 prevents trauma-induced heterotopic ossification.Scientific reports · 2016Article
- Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression.Cellular signalling · 2016Article
- Connexins in the skeleton.Seminars in cell & developmental biology · 2016Review
- A Functional Assay to Assess Connexin 43-Mediated Cell-to-Cell Communication of Second Messengers in Cultured Bone Cells.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Article
- Connexins and pannexins in the skeleton: gap junctions, hemichannels and more.Cellular and molecular life sciences : CMLS · 2015Review
- Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis.Journal of shoulder and elbow surgery · 2015Article
- Connexin43 enhances the expression of osteoarthritis-associated genes in synovial fibroblasts in culture.BMC musculoskeletal disorders · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In this study, we examine the role of the gap junction protein, connexin43 (Cx43), in the transcriptional response of osteocalcin to fibroblast growth factor 2 (FGF2) in MC3T3 osteoblasts. By luciferase reporter assays, we identify that the osteocalcin transcriptional response to FGF2 is markedly increased by overexpression of Cx43, an effect that is mediated by Runx2 via its OSE2 cognate element, but not by a previously identified connexin-responsive Sp1/Sp3-binding element. Furthermore, disruption of Cx43 function with Cx43 siRNAs or overexpression of connexin45 markedly attenuates the response to FGF2. Inhibition of protein kinase C delta (PKCdelta) with rottlerin or siRNA-mediated knockdown abrogates the osteocalcin response to FGF2. Additionally, we show that upon treatment with FGF2, PKCdelta translocates to the nucleus, PKCdelta and Runx2 are phosphorylated and these events are enhanced by Cx43 overexpression, suggesting that the degree of activation is enhanced by increased Cx43 levels. Indeed, chromatin immunoprecipitations of the osteocalcin proximal promoter with antibodies against Runx2 demonstrate that the recruitment of Runx2 to the osteocalcin promoter in response to FGF2 treatment is dramatically enhanced by Cx43 overexpression. Thus, Cx43 plays a critical role in regulating the ability of osteoblasts to respond to FGF2 by impacting PKCdelta and Runx2 function.
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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.