ArticleiScience2024
Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
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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.
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Who cites it
9 citing papers in PubMed.
- Early targeting of the YAP/TEAD-PKC-NF-κB axis alleviates post-traumatic osteoarthritis.iScience · 2026Article
- Compressive stress-driven mechanosignaling in chondrocytes: From molecular mechanism to scaffold engineering and translational opportunities.Materials today. Bio · 2026Review
- Ceramide-PKCζ signaling axis mediates burn-enhanced ectopic calcification during Achilles tendon healing.Journal of molecular histology · 2026Article
- Hippo-YAP/TAZ Signaling in Astrocytes and Microglia: Role in Neuroinflammation, Neurodegeneration and Glial Tumors.International journal of molecular sciences · 2026Review
- Triamcinolone Modulates Chondrocyte Biomechanics and Calcium-Dependent Mechanosensitivity.International journal of molecular sciences · 2026Article
- Effect of distraction length on the morphology of knee cartilage in a rat model of femoral distraction osteogenesis.Frontiers in physiology · 2026Article
- 4D Biofabrication of Magnetically Augmented Callus Assembloid Implants Enables Rapid Endochondral Ossification via Activation of Mechanosensitive Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach.Biomedicines · 2024Review
- Interplay of Glucose Metabolism and Hippo Pathway in Chondrocytes: Pathophysiology and Therapeutic Targets.Bioengineering (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Recent studies have implicated a crucial role of Hippo signaling in cell fate determination by biomechanical signals. Here we show that mechanical loading triggers the activation of a Hippo-PKCζ-NFκB pathway in chondrocytes, resulting in the expression of NFκB target genes associated with inflammation and matrix degradation. Mechanistically, mechanical loading activates an atypical PKC, PKCζ, which phosphorylates NFκB p65 at Serine 536, stimulating its transcriptional activation. This mechanosensitive activation of PKCζ and NFκB p65 is impeded in cells with gene deletion or chemical inhibition of Hippo core kinases LATS1/2, signifying an essential role of Hippo signaling in this mechanotransduction. A PKC inhibitor AEB-071 or PKCζ knockdown prevents p65 Serine 536 phosphorylation. Our study uncovers that the interplay of the Hippo signaling, PKCζ, and NFκB in response to mechanical loading serves as a therapeutic target for knee osteoarthritis and other conditions resulting from mechanical overloading or Hippo signaling deficiencies.
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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 Socratic graph.