ArticleBMC musculoskeletal disorders2014
Connexin43 enhances the expression of osteoarthritis-associated genes in synovial fibroblasts in culture.
Article in BMC musculoskeletal disorders, 2014. 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.
- Loosening the Lid on Shoulder Osteoarthritis: How the Transcriptome and Metabolic Syndrome Correlate with End-Stage Disease.International journal of molecular sciences · 2025Article
- Adipose mesenchymal stem cells-derived exosomes alleviate osteoarthritis by transporting microRNA -376c-3p and targeting the WNT-beta-catenin signaling axis.Apoptosis : an international journal on programmed cell death · 2023Article
- Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence.International journal of molecular sciences · 2023Article
- Toward defining the role of the synovium in mitigating normal articular cartilage wear and tear.Journal of biomechanics · 2023Article
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression.Cell death & disease · 2022Article
- Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes.Biology · 2022Review
- Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading.eLife · 2022Article
- ATP transporters in the joints.Purinergic signalling · 2021Review
- The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: An update.Journal of cellular and molecular medicine · 2020Review
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- Angiotensin II induces RAW264.7 macrophage polarization to the M1‑type through the connexin 43/NF‑κB pathway.Molecular medicine reports · 2020Article
- Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.Pflugers Archiv : European journal of physiology · 2019Article
- Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.Biochemical and biophysical research communications · 2019Article
- Intercellular communication via gap junction channels between chondrocytes and bone cells.Biochimica et biophysica acta. Biomembranes · 2018Article
- Epigenetics and bone diseases.Genetics research · 2018Review
- Senescent cells and osteoarthritis: a painful connection.The Journal of clinical investigation · 2018Review
- Biochemical alterations in inflammatory reactive chondrocytes: evidence for intercellular network communication.Heliyon · 2018Article
- Joint diseases: from connexins to gap junctions.Nature reviews. Rheumatology · 2017Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRecent work has shown that the gap junction protein connexin43 (Cx43) is upregulated in cells of the joint during osteoarthritis (OA). Here we examined if the OA-associated increase in Cx43 expression impacts the function of synovial fibroblasts by contributing to the production of catabolic and inflammatory factors that exacerbate joint destruction in arthritic disease.
methodsUsing rabbit and human synovial fibroblast cell lines, we examined the effects of Cx43 overexpression and Cx43 siRNA-mediated knockdown on the gene expression of OA-associated matrix metalloproteinases (MMP1 and MMP13), aggrecanases (ADAMTS4 and ADAMTS5), and inflammatory factors (IL1, IL6 and PTGS2) by quantitative real time RT-PCR. We examined collagenase activity in conditioned media of cultured synovial cells following Cx43 overexpression. Lastly, we assessed the interplay between Cx43 and the NFκB cascade by western blotting and gene expression studies.
resultsIncreasing Cx43 expression enhanced the gene expression of MMP1, MMP13, ADAMTS4, ADAMTS5, IL1, IL6 and PTGS2 and increased the secretion of collagenases into conditioned media of cultured synovial fibroblasts. Conversely, knockdown of Cx43 decreased expression of many of these catabolic and inflammatory genes. Modulation of Cx43 expression altered the phosphorylation of the NFκB subunit, p65, and inhibition of NFκB with chemical inhibitors blocked the effects of increased Cx43 expression on the mRNA levels of a subset of these catabolic and inflammatory genes.
conclusionsIncreasing or decreasing Cx43 expression alone was sufficient to alter the levels of catabolic and inflammatory genes expressed by synovial cells. The NFκB cascade mediated the effect of Cx43 on the expression of a subset of these OA-associated genes. As such, Cx43 may be involved in joint pathology during OA, and targeting Cx43 expression or function may be a viable therapeutic strategy to attenuate the catabolic and inflammatory environment of the joint during OA.
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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.