ArticleCell discovery2022
A novel prostaglandin E receptor 4 (EP4) small molecule antagonist induces articular cartilage regeneration.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
The trial behind it
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- MnOMaterials today. Bio · 2026Article
- Selective EP4 Receptor Antagonism for Osteoarthritis Pain: Emerging Evidence and Future Directions for KF-0210.Pain and therapy · 2026Review
- Dietary omega-6 lipids promote postinjury aberrant bone formation in obesity.The Journal of clinical investigation · 2026Article
- Therapeutic Potential of Ambroxol in Osteoarthritis: A Drug Repurposing Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration.Science (New York, N.Y.) · 2026Article
- Local delivery of OSK factors enables partial cellular reprogramming to mitigate osteoarthritis and cartilage fibrosis.Experimental & molecular medicine · 2026Article
- Rab23 GTPase and IFT43 regulate the trafficking of prostaglandin E receptor 4 to primary cilia.Communications biology · 2025Article
- Conservative Management of Focal Chondral Lesions of the Knee and Ankle: Current Concepts.Cells · 2025Review
- A Review of Rodent Behavior, Mobility, and Pain Modifications in Response to Destabilization of the Medial Meniscus Injury.Biomedicines · 2025Review
- MaskMol: knowledge-guided molecular image pre-training framework for activity cliffs with pixel masking.BMC biology · 2025Article
- Amygdalin and magnesium ions exert synergistic effects on cartilage regeneration by inhibiting chondrocyte ferroptosis via the IL-17/GPX4 axis.Journal of orthopaedic translation · 2025Article
- Hypothalamus Regulates Anabolic Metabolism of Articular Cartilage Superficial Chondrocytes through PGE2 Skeletal Interoception.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dual Roles of Prostaglandin E2 (PGE2) in Bone Remodeling and Pain Management: Bridging the Gap in Osteoarthritis Research.Mediators of inflammation · 2025Review
- The Role of PGE2 in Age-related Diseases.Current drug targets · 2025Review
- Biomaterial design for regenerating aged bone: materiobiological advances and paradigmatic shifts.National science review · 2024Review
- DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.Nature aging · 2024Article
- Skeletal interoception in osteoarthritis.Bone research · 2024Review
- Articular cartilage repair biomaterials: strategies and applications.Materials today. Bio · 2024Review
- Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Articular cartilage repair and regeneration is an unmet clinical need because of the poor self-regeneration capacity of the tissue. In this study, we found that the expression of prostaglandin E receptor 4 (PTGER4 or EP4) was largely increased in the injured articular cartilage in both humans and mice. In microfracture (MF) surgery-induced cartilage defect (CD) and destabilization of the medial meniscus (DMM) surgery-induced CD mouse models, cartilage-specific deletion of EP4 remarkably promoted tissue regeneration by enhancing chondrogenesis and cartilage anabolism, and suppressing cartilage catabolism and hypertrophy. Importantly, knocking out EP4 in cartilage enhanced stable mature articular cartilage formation instead of fibrocartilage, and reduced joint pain. In addition, we identified a novel selective EP4 antagonist HL-43 for promoting chondrocyte differentiation and anabolism with low toxicity and desirable bioavailability. HL-43 enhanced cartilage anabolism, suppressed catabolism, prevented fibrocartilage formation, and reduced joint pain in multiple pre-clinical animal models including the MF surgery-induced CD rat model, the DMM surgery-induced CD mouse model, and an aging-induced CD mouse model. Furthermore, HL-43 promoted chondrocyte differentiation and extracellular matrix (ECM) generation, and inhibited matrix degradation in human articular cartilage explants. At the molecular level, we found that HL-43/EP4 regulated cartilage anabolism through the cAMP/PKA/CREB/Sox9 signaling. Together, our findings demonstrate that EP4 can act as a promising therapeutic target for cartilage regeneration and the novel EP4 antagonist HL-43 has the clinical potential to be used for cartilage repair and regeneration.
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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.