ArticleArthritis & rheumatology (Hoboken, N.J.)2014
Cyclin-dependent kinase 9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- TNFα-Related Chondrocyte Inflammation Models: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- CDK7, CDK9, or CDK11 inhibition reduces neutrophil-driven inflammation and tissue damage in experimental autoimmune models.Cell communication and signaling : CCS · 2026Article
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Repurposing flavopiridol as an inhaled therapeutic for pulmonary fibrosis.European journal of pharmacology · 2025Article
- CircFUNDC1 interacts with CDK9 to promote mitophagy in nucleus pulposus cells under oxidative stress and ameliorates intervertebral disc degeneration.Cell death & disease · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Cbx4 SUMOylates BRD4 to regulate the expression of inflammatory cytokines in post-traumatic osteoarthritis.Experimental & molecular medicine · 2024Article
- Tofacitinib Monotherapy in Rheumatoid Arthritis: Clinical Trials and Real-World Data Contextualization of Patients, Efficacy, and Treatment Retention.Open access rheumatology : research and reviews · 2024Article
- The Pharmacological Implications of Flavopiridol: An Updated Overview.Molecules (Basel, Switzerland) · 2023Review
- Intra-articular injection of flavopiridol-loaded microparticles for treatment of post-traumatic osteoarthritis.Acta biomaterialia · 2022Article
- Identifying small molecules for protecting chondrocyte function and matrix integrity after controlled compressive injury.Osteoarthritis and cartilage open · 2022Article
- Production of Inhalable Ultra-Small Particles for Delivery of Anti-Inflammation Medicine via a Table-Top Microdevice.Micromachines · 2022Article
- Selective Cdk9 inhibition resolves neutrophilic inflammation and enhances cardiac regeneration in larval zebrafish.Development (Cambridge, England) · 2022Article
- Article
- Bromodomain-containing-protein-4 and cyclin-dependent-kinase-9 inhibitors interact synergistically in vitro and combined treatment reduces post-traumatic osteoarthritis severity in mice.Osteoarthritis and cartilage · 2021Article
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Atuveciclib Suppresses Intervertebral Disk Degeneration via the Inhibition of the NF-κB Signaling Pathway.Frontiers in cell and developmental biology · 2020Article
- Cyclin-dependent kinase 9 expression and its association with CD8Oncology letters · 2019Article
- Transcription modulation by CDK9 regulates inflammatory genes and RIPK3-MLKL-mediated necroptosis in periodontitis progression.Scientific reports · 2019Article
- Inflammation Resolution and the Induction of Granulocyte Apoptosis by Cyclin-Dependent Kinase Inhibitor Drugs.Frontiers in pharmacology · 2019Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
objectiveCyclin-dependent kinase 9 (CDK-9) controls the activation of primary inflammatory response genes. The purpose of this study was to determine whether CDK-9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.
methodsHuman chondrocytes were challenged with different proinflammatory stimuli (interleukin-1β [IL-1β], lipopolysaccharides, and tumor necrosis factor α) in the presence or absence of either the CDK-9 inhibitor flavopiridol or small interfering RNA (siRNA). The expression of messenger RNA (mRNA) for inflammatory mediator genes, catabolic genes, and anabolic genes were determined by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Cartilage explants were incubated for 6 days with IL-1β in the presence or absence of flavopiridol. Cartilage matrix degradation was assessed by the release of glycosaminoglycan (GAG) and cleaved type II collagen (COL2A) peptides.
resultsCDK-9 inhibition by flavopiridol or knockdown by siRNA effectively suppressed the induction of mRNA for inducible nitric oxide synthase by all 3 proinflammatory stimuli. Results from NF-κB-targeted PCR array analysis showed that flavopiridol suppressed IL-1β induction of a broad range of inflammatory mediator genes (59 of 67 tested). CDK-9 inhibition also suppressed the induction of catabolic genes (matrix metalloproteinase 1 [MMP-1], MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5), but did not affect the basal expression of anabolic genes (COL2A, aggrecan, and cartilage oligomeric matrix protein) and housekeeping genes. Flavopiridol had no apparent short-term cytotoxicity, as assessed by G6PDH activity. Finally, in IL-1β-treated cartilage explants, flavopiridol reduced the release of the matrix degradation product GAG and cleaved COL2A peptides, but did not affect long-term chondrocyte viability.
conclusionCDK-9 activity is required for the primary inflammatory response in chondrocytes. Flavopiridol suppresses the induction of inflammatory mediator genes and catabolic genes to protect cartilage from the deleterious effects of proinflammatory cytokines, without affecting cell viability and functions.
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.