ArticleJCI insight2023
Mocetinostat activates Krüppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- ESCRT-0 regulates AMPA receptor currents and CabioRxiv : the preprint server for biology · 2026Article
- PrPStem cell reports · 2026Article
- Deficiency of Krüppel-like factor 15 activates β-catenin and is involved in the development of osteoarthritis : Author.Arthritis research & therapy · 2026Article
- Article
- Class I histone deacetylases and their inhibitors as targets to modulate cellular senescence in osteoarthritis.GeroScience · 2026Article
- HDAC1 modulates sepsis-induced immunosuppression by driving the exhaustion of CD8+ T cells.JCI insight · 2026Article
- Xinfeng capsule improves hyperinflammation-associated hypercoagulability and self-perception in osteoarthritis by regulating KLF4 through METTL14-mediated mFrontiers in immunology · 2026Article
- Review
- HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes.Inflammation · 2025Article
- Knee Osteoarthritis: Current Insights Into Pathophysiology and Non-surgical Management Options.Cureus · 2025Review
- The role and mechanism of transcription factor KLF4 in regulating mitochondrial damage and apoptosis by activating chondrocyte autophagy in osteoarthritis.Scientific reports · 2025Article
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- Comprehensive Investigation of a Tyrosine Kinase Inhibitor-Resistant GeneWorld journal of oncology · 2025Article
- Review
- Histone Deacetylase (HDAC) Inhibitors as a Novel Therapeutic Option Against Fibrotic and Inflammatory Diseases.Biomolecules · 2024Review
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.Annals of medicine and surgery (2012) · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Osteoarthritis (OA) is the most common joint disorder, and disease-modifying OA drugs (DMOADs) represent a major need in OA management. Krüppel-like factor 4 (KLF4) is a central transcription factor upregulating regenerative and protective functions in joint tissues. This study was aimed to identify small molecules activating KLF4 expression and to determine functions and mechanisms of the hit compounds. High-throughput screening (HTS) with 11,948 clinical-stage compounds was performed using a reporter cell line detecting endogenous KLF4 activation. Eighteen compounds were identified through the HTS and confirmed in a secondary screen. After testing in SW1353 chondrosarcoma cells and human chondrocytes, mocetinostat - a class I selective histone deacetylase (HDAC) inhibitor - had the best profile of biological activities. Mocetinostat upregulated cartilage signature genes in human chondrocytes, meniscal cells, and BM-derived mesenchymal stem cells, and it downregulated hypertrophic, inflammatory, and catabolic genes in those cells and synoviocytes. I.p. administration of mocetinostat into mice reduced severity of OA-associated changes and improved pain behaviors. Global gene expression and proteomics analyses revealed that regenerative and protective effects of mocetinostat were dependent on peroxisome proliferator-activated receptor γ coactivator 1-α. These findings show therapeutic and protective activities of mocetinostat against OA, qualifying it as a candidate to be used as a DMOAD.
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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.