Ann N Y Acad Sci. 2006 Apr;1068:214-24.
Role of connexin43 in osteoblast response to physical load.
Abstract
Gap junctions are hexameric transmembrane channels formed by connexins,
and are responsible for direct cell-to-cell communication. The most
abundant gap junction protein in bone is connexin43 (Cx43), although
connexin45 (Cx45) is also expressed.
In the present study, we tested the hypothesis that bone cell responses to mechanical stimulation are dependent on the type of gap junction communication provided by Cx43 in vitro and in an in vivo model of physical load.
Application of cyclic stretch to calvaria osteoblasts results in a modest but detectable increase in PGE2 levels, and the amount of PGE2 produced was lower in cells isolated from Cx43 null mice. Mice with an osteoblast-specific deletion of the Cx43 gene were subjected to an in vivo four-point bending protocol on the tibia. This resulted in fast and exuberant formation of woven bone at the region directly below the loading fulcrum in both osteoblast Cx43-deleted and wild-type mice. However, indirect measurement of endosteal bone apposition suggested a less pronounced effect of physical load in Cx43-deficient than in wild-type mice. Taken together, these results indicate that deficiency of Cx43 in osteoblasts attenuates but does not abolish anabolic responses to mechanical strain.
In the present study, we tested the hypothesis that bone cell responses to mechanical stimulation are dependent on the type of gap junction communication provided by Cx43 in vitro and in an in vivo model of physical load.
Application of cyclic stretch to calvaria osteoblasts results in a modest but detectable increase in PGE2 levels, and the amount of PGE2 produced was lower in cells isolated from Cx43 null mice. Mice with an osteoblast-specific deletion of the Cx43 gene were subjected to an in vivo four-point bending protocol on the tibia. This resulted in fast and exuberant formation of woven bone at the region directly below the loading fulcrum in both osteoblast Cx43-deleted and wild-type mice. However, indirect measurement of endosteal bone apposition suggested a less pronounced effect of physical load in Cx43-deficient than in wild-type mice. Taken together, these results indicate that deficiency of Cx43 in osteoblasts attenuates but does not abolish anabolic responses to mechanical strain.
- PMID:
- 16831921
- DOI:
- 10.1196/annals.1346.023
Konneksiini43 geeni
https://www.ncbi.nlm.nih.gov/gene/2697
- Official Symbol
- GJA1provided by HGNC
- Official Full Name
- gap junction protein alpha 1provided by HGNC
- Primary source
- HGNC:HGNC:4274
- See related
- Ensembl:ENSG00000152661 MIM:121014; Vega:OTTHUMG00000015479
- Gene type
- protein coding
- RefSeq status
- REVIEWED
- Organism
- Homo sapiens
- Lineage
- Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
- Also known as
- HSS; CMDR; CX43; EKVP; GJAL; ODDD; AVSD3; HLHS1; PPKCA
- Summary
- This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. The encoded protein is the major protein of gap junctions in the heart that are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. A related intronless pseudogene has been mapped to chromosome 5. Mutations in this gene have been associated with oculodentodigital dysplasia, autosomal recessive craniometaphyseal dysplasia and heart malformations.
- Kromosomi 6q22.31
ARTIKKELEITA tämän konneksiini43:n merkityksestä.
Related articles in PubMed
- High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43. Yu H, et al. Exp Cell Res, 2016 Mar 1. PMID 26902399
- AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis. Zhang X, et al. Sci Rep, 2016 Jan 25. PMID 26806558, Free PMC Article
- Connexin 43 Affects Osteogenic Differentiation of the Posterior Longitudinal Ligament Cells via Regulation of ERK Activity by Stabilizing Runx2 in Ossification. Yang H, et al. Cell Physiol Biochem, 2016. PMID 26784020
- Increased expression of CX43 on stromal cells promotes leukemia apoptosis. Yang S, et al. Oncotarget, 2015 Dec 29. PMID 26517241, Free PMC Article
- All-trans retinoic acid arrests cell cycle in leukemic bone marrow stromal cells by increasing intercellular communication through connexin 43-mediated gap junction. Liu Y, et al. J Hematol Oncol, 2015 Oct 7. PMID 26446715, Free PMC Article
GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
- AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction.
- Cx43, which is up-regulated by mechanical stress, seems to function partly via the activation of ERK1/2 and p38 MAPK signals to promote the osteoblastic differentiation of ligament fibroblasts.
- Cx43 expressed by mesenchymal stem cells induces apoptosis on leukemia cells.
- Report expression of connexin 43 in ovarian cancer cells in G1/S phase.
- Connexin 43 significantly regulates osteogenic differentiation in the cells from posterior longitudinal ligament by altering the activity of ERK, and subsequently causing the modification of Runx2.
- Our data suggest a mechanism by which CT-Cx43 may regulate cell proliferation by regulating mir-125b and p53 expression
- we are the first to identify that miR-381 suppresses C/EBPalpha-dependent Cx43 expression in breast cancer cells. The miR-381-C/EBPalpha-Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer
- Cx43-Hsc70 interaction regulates cell cycle G1/S progression through a novel mechanism by which Cx43-Hsc70 interaction prevents the nuclear accumulation of p27 through controlling the nuclear translocation of cyclin D1-CDK4-p27 complex.
- local regulation of endothelial Cx43 expression within the vasculature regulates monocyteendothelial adhesion.demonstrate a specific role of the upstream DNA methylation/miR-1298/Connexin 43 pathway in regulating VSMC function
- KONNEKSIINEISTÄ YLEISTIETOA
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