ArticleJournal of orthopaedic surgery and research2019
Recruitment of Brd3 and Brd4 to acetylated chromatin is essential for proinflammatory cytokine-induced matrix-degrading enzyme expression.
Article in Journal of orthopaedic surgery and research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Integrated Multi-Omics Analysis and Experimental Validation Identify Acetylation-Related Genes as Potential Regulators in Osteoarthritis.Biomedicines · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Development of cell-active BRD4-D1 selective inhibitors to decode the role of BET proteins in LPS-mediated liver inflammation.European journal of medicinal chemistry · 2026Article
- Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential.Journal of inflammation (London, England) · 2026Review
- Decoding Epigenetic Switches: How Histone Acetylation/Deacetylation Regulates Mononuclear/Macrophage Fate in Bone Disorders.International journal of biological sciences · 2026Review
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- Loss of Brd4 alleviates pathological bone loss via Slc9b2 suppression in osteoclastogenesis.Clinical and translational medicine · 2025Article
- A Novel BD2-Selective Inhibitor of BRDs Mitigates ROS Production and OA Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Article
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression.Regenerative therapy · 2023Article
- BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts.Biomedicines · 2023Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.Frontiers in cell and developmental biology · 2021Review
- A Novel Approach to Safer Glucocorticoid Receptor-Targeted Anti-lymphoma Therapy via REDD1 (Regulated in Development and DNA Damage 1) Inhibition.Molecular cancer therapeutics · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundProinflammatory cytokines, which can upregulate the expression of matrix-degrading enzymes in chondrocytes, play important roles in the development of osteoarthritis. BET family proteins, acting as the "readers" of acetylated modifications on histones, have been linked to transcriptional regulation. And a BET protein inhibitor, I-BET151, has been shown to inhibit the induction of matrix-degrading enzymes by proinflammatory cytokines in chondrocytes. Our objective is to clarify the role and mechanism of BET proteins on matrix-degrading enzyme gene expression by using a human chondrosarcoma cell line (SW1353).
methodsWe pretreated SW1353 cells with I-BET151 prior to treatment with IL-1β or TNF-α and then checked the expression of four matrix-degrading enzyme genes (MMP1, MMP3, MMP13, and ADAMTS4). We performed knockdown of BET protein family members (BRD2, BRD3, and BRD4) with corresponding siRNAs in SW1353 cells prior to treatment with IL-1β or TNF-α and checked the expression of the matrix-degrading enzyme genes. We evaluated Brd-mediated transcriptional regulation on the matrix-degrading enzyme genes by ChIP assay.
resultsWe confirmed that I-BET151 could suppress the IL-1β- or TNF-α-induced expression of MMP1, MMP3, MMP13, and ADAMTS4 in SW1353 cells. Brd3 and Brd4 were required for the IL-1β- or TNF-α-induced expression of matrix-degrading enzyme genes in SW1353 cells. We revealed that inducible acetylation of H4k5/8/12 and the recruitment of Brd3, Brd4, and p-TEFb to chromatin were involved in IL-1β- or TNF-α-induced transcription.
conclusionsOur findings suggested that Brd3 and Brd4 were essential for the IL-1β- or TNF-α-induced transcription of matrix-degrading enzyme genes, and recruitment of Brd3 and Brd4 to chromatin of these genes played the main role in this process.
Indexed as
Identifiers
What OpenQuestion holds
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.