ArticleJournal of cellular biochemistry2023
The epigenetic regulator BRD4 is required for myofibroblast differentiation of knee fibroblasts.
Article in Journal of cellular biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential.Journal of inflammation (London, England) · 2026Review
- New Clues to the Challenge of Knee Arthrofibrosis: From Molecules to Therapies.The Journal of the American Academy of Orthopaedic Surgeons · 2026Review
- Temporal- and concentration-dependent effects of transforming growth factor-beta 1 (TGF-β1) in primary human knee fibroblasts.Bone & joint research · 2025Article
- Multi-Omics insights into the molecular mechanisms of trochlear dysplasia: A proteomic and metabolomic study in rats.PloS one · 2025Article
- AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.Journal of cellular physiology · 2024Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Arthrofibrosis, which is characterized by excessive scar tissue and limited motion, can complicate the daily functioning of patients after total knee arthroplasty (TKA). Molecular hallmarks of arthrofibrosis include pathologic accumulation of myofibroblasts and disproportionate collagen deposition. Epigenetic mechanisms, including posttranslation modification of histones, control gene expression and may regulate fibrotic events. This study assessed the role of the bromodomain and extra-terminal (BET) proteins on myofibroblast differentiation. This group of epigenetic regulators recognize acetylated lysines and are targeted by a class of drugs known as BET inhibitors. RNA-seq analysis revealed robust mRNA expression of three BET members (BRD2, BRD3, and BRD4) while the fourth member (BRDT) is not expressed in primary TKA knee outgrowth fibroblasts. RT-qPCR and western blot analyses revealed that BET inhibition with the small molecule JQ1 impairs TGFβ1-induced expression of ACTA2, a key myofibroblast marker, in primary outgrowth knee fibroblasts. Similarly, JQ1 administration also reduced COL3A1 mRNA levels and collagen deposition as monitored by picrosirius red staining. Interestingly, the inhibitory effects of JQ1 on ACTA2 mRNA and protein expression, as well as COL3A1 expression and collagen deposition, were paralleled by siRNA-mediated depletion of BRD4. Together, these data reveal that BRD4-mediated epigenetic events support TGFβ1-mediated myofibroblast differentiation and collagen deposition as seen in arthrofibrosis. To our knowledge, these are the first studies that assess epigenetic regulators and their downstream events in the context of arthrofibrosis. Future studies may reveal clinical utility for drugs that target epigenetic pathways, specifically BET proteins, in the prevention and treatment of arthrofibrosis.
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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.