ArticleGenes & development2014
Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 135 citations in OpenAlex.
- Motion as Medicine: Physical Activity, Joint Sensitivity, and Pain Management-A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Loss of mechanical stress induces synovitis, fibrosis and articular cartilage degeneration via distinct synovial cell subsets.Scientific reports · 2026Article
- Lubricin in osteoarthritis: functions and therapeutic prospects.Frontiers in immunology · 2026Review
- Ultrasound-responsive hydrogels for bone and cartilage tissue engineering.Materials today. Bio · 2025Review
- Optical Redox Imaging Predicts Post-Loading Cartilage Mitochondrial Membrane Potential.Annals of biomedical engineering · 2025Article
- Tensile stress promotes the chondrogenic ability of condylar cartilage stem/progenitor cells in the temporomandibular joint via the Piezo1-CaStem cell research & therapy · 2025Article
- Review
- A conserved transcription factor regulatory program promotes tendon fate.Developmental cell · 2024Article
- Regenerative capacity of human pluripotent stem cell-derived articular chondrocytes in vitro.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- Prg4-Expressing Chondroprogenitor Cells in the Superficial Zone of Articular Cartilage.International journal of molecular sciences · 2024Review
- Histological and immunohistochemical analyses of articular cartilage during onset and progression of pre- and early-stage osteoarthritis in a rodent model.Scientific reports · 2024Article
- Structural and Molecular Changes of Human Chondrocytes Exposed to the Rotating Wall Vessel Bioreactor.Biomolecules · 2023Article
- Regeneration of joint surface defects by transplantation of allogeneic cartilage: application of iPS cell-derived cartilage and immunogenicity.Inflammation and regeneration · 2023Review
- Low-intensity pulsed ultrasound irradiation attenuates collagen degradation of articular cartilage in early osteoarthritis-like model mice.Journal of experimental orthopaedics · 2023Article
- Effect of Moderate Exercise on the Superficial Zone of Articular Cartilage in Age-Related Osteoarthritis.Diagnostics (Basel, Switzerland) · 2023Article
- Notch Signaling Regulates the Chondrogenic Potential of Both Articular Chondrocytes and Their Progenitors During Expansion.Stem cells (Dayton, Ohio) · 2023Article
- Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect.Nature communications · 2023Article
- Osteoarthritis: pathogenic signaling pathways and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Mechanisms of tissue degeneration mediated by periostin in spinal degenerative diseases and their implications for pathology and diagnosis: a review.Frontiers in medicine · 2023Review
- HU308 Mitigates Osteoarthritis by Stimulating Sox9-Related Networks of Carbohydrate Metabolism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lubricin is a secreted proteoglycan encoded by the Prg4 locus that is abundantly expressed by superficial zone articular chondrocytes and has been noted to both be sensitive to mechanical loading and protect against the development of osteoarthritis. In this study, we document that running induces maximal expression of Prg4 in the superficial zone of knee joint articular cartilage in a COX-2-dependent fashion, which correlates with augmented levels of phospho-S133 CREB and increased nuclear localization of CREB-regulated transcriptional coactivators (CRTCs) in this tissue. Furthermore, we found that fluid flow shear stress (FFSS) increases secretion of extracellular PGE2, PTHrP, and ATP (by epiphyseal chondrocytes), which together engage both PKA- and Ca(++)-regulated signaling pathways that work in combination to promote CREB-dependent induction of Prg4, specifically in superficial zone articular chondrocytes. Because running and FFSS both boost Prg4 expression in a COX-2-dependent fashion, our results suggest that mechanical motion may induce Prg4 expression in the superficial zone of articular cartilage by engaging the same signaling pathways activated in vitro by FFSS that promote CREB-dependent gene expression in this tissue.
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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.