ArticleAnnals of the rheumatic diseases2023
Targeting FoxO transcription factors with HDAC inhibitors for the treatment of osteoarthritis.
Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Identification of Mitochondrial Dynamics-Related Genes as Diagnostic Biomarkers for Osteoarthritis Using Weighted Gene Co-expression Network Analysis and Machine Learning.Clinics in orthopedic surgery · 2026Article
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- SHH drives gastric cancer-associated fibroblast activation via ACLY-dependent acetyl-CoA metabolism and histone acetylation.Discover oncology · 2026Article
- HDAC3 represses Nrf2-GDF11 signaling to drive chondrocyte adipogenesis in temporomandibular joint osteoarthritis.Journal of advanced research · 2026Article
- HDAC9 drives intervertebral disc degeneration by potentiating STAT1-mediated senescence and inflammation.Journal of orthopaedic surgery and research · 2026Article
- UCHL1 enhancesHistology and histopathology · 2026Article
- Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtDNA.Bioactive materials · 2026Article
- Dual epigenetic and nuclear export inhibition by chidamide and selinexor in high grade B-cell lymphomas via survivin and PI3K/AKT inhibition.Clinical epigenetics · 2026Article
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- Nanotherapeutic Strategies for Osteoarthritis: Targeting Aging, Metabolism and Inflammation.International journal of nanomedicine · 2026Review
- Microenvironmental response-based treatment of osteoarthritis is a highly effective and durable program: a review.Journal of orthopaedic surgery and research · 2025Review
- Repurposing the antihistamine cyproheptadine for osteoarthritis: nothing to sneeze at.The Journal of clinical investigation · 2025Article
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- Detumescence Analgesic Plaster mitigates knee osteoarthritis via active ingredients targeting mitochondrial complex 1/AMPK/MYL3-regulated cartilage homeostasis.Chinese medicine · 2025Article
- O-GlcNAc transferase influences the progression of degenerative cartilage disease in lumbar facet joint osteoarthritis through FoxO1 and EGR1.Cell death discovery · 2025Article
- Review
- Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025Review
- Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise.International journal of molecular sciences · 2025Review
- Extracellular vesicles from adipose-derived stromal/stem cells reprogram dendritic cells to alleviate rat TMJOA by transferring mitochondria.Journal of nanobiotechnology · 2025Article
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesOsteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4). The objective of this study was to identify small molecules that can increase FoxO1 expression.
methodsWe constructed a reporter cell line with FoxO1 promoter sequences and performed high-throughput screening (HTS) of the Repurposing, Focused Rescue and Accelerated Medchem (ReFRAME) library . Hits from the HTS were validated and function was assessed in human chondrocytes, meniscus cells and synoviocytes and following administration to mice. The most promising hit, the histone deacetylase inhibitor (HDACI) panobinostat was tested in a murine OA model.
resultsAmong the top hits were HDACI and testing in human chondrocytes, meniscus cells and synoviocytes showed that panobinostat was the most promising compound as it increased the expression of autophagy genes and PRG4 while suppressing the basal and IL-1β induced expression of inflammatory mediators and extracellular matrix degrading enzymes. Intraperitoneal administration of panobinostat also suppressed the expression of mediators of OA pathogenesis induced by intra-articular injection of IL-1β. In a murine OA model, panobinostat reduced the severity of histological changes in cartilage, synovium and subchondral bone and improved pain behaviours.
conclusionPanobinostat has a clinically relevant activity profile and is a candidate for OA symptom and structure modification.
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