ArticleProceedings of the National Academy of Sciences of the United States of America2014
TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 295 papers, 2 of them syntheses that pooled it.
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Who cites it
295 citing papers in PubMed, 2 syntheses or guidelines pooled it, 472 citations in OpenAlex.
- Standardized Effect Measures Informing Next-Generation Strategies for Mechanical Stimulation in Cartilage Tissue Engineering.Advanced healthcare materials · 2026Pooled it
- Macrophage mechanobiology: from sensing to disease.Frontiers in immunology · 2026Pooled it
- Increasing dynamic limb-level loading via real-time biofeedback decreases cumulative loading impulse during gait post-anterior cruciate ligament reconstruction.Clinical biomechanics (Bristol, Avon) · 2026Article
- Decoding intervertebral disc degeneration pathomechanics: from mechanisms to therapeutic horizons.Journal of advanced research · 2026Review
- From Joint Loading to Osteoarthritis: A Multiscale Review of Knee Mechanobiology and Digital Modelling.International journal of molecular sciences · 2026Review
- A multiscale modeling approach to study the role of mechanics and inflammation in the pathophysiology of articular cartilage.Computers in biology and medicine · 2026Article
- Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease.The FEBS journal · 2026Review
- The Influence of the Chondrocyte Microenvironment on Multiscale Articular Cartilage Mechanics: A Computational Study.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Graded ankle instability induces early osteoarthritic changes in a rat model.Osteoarthritis and cartilage open · 2026Article
- Biophysical signal-driven scaffold design for stem cell-guided osteochondral regeneration.Bioactive materials · 2026Review
- PIEZO1 variants that reduce open channel probability are associated with familial osteoarthritis.The Journal of biological chemistry · 2026Article
- Identification of a new population of TnnBone research · 2026Article
- Bioreactor-Induced Compression in Scaffolds for the Enhancement of Cartilage Regeneration: A Systematic Review.Annals of biomedical engineering · 2026Review
- Article
- Micro-nano integrated platforms for osteoarthritis therapy: From spatial manipulation to cellular reprogramming.Materials today. Bio · 2026Review
- The osteochondral regeneration paradox: why biomimetic scaffolds are biologically superior but injectable systems dominate the clinic.RSC advances · 2026Review
- The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function.Biomedicines · 2026Review
- A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells.Stem cell research & therapy · 2026Article
- Review
235 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
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Abstract
Mechanical loading of joints plays a critical role in maintaining the health and function of articular cartilage. The mechanism(s) of chondrocyte mechanotransduction are not fully understood, but could provide important insights into new physical or pharmacologic therapies for joint diseases. Transient receptor potential vanilloid 4 (TRPV4), a Ca(2+)-permeable osmomechano-TRP channel, is highly expressed in articular chondrocytes, and loss of TRPV4 function is associated with joint arthropathy and osteoarthritis. The goal of this study was to examine the hypothesis that TRPV4 transduces dynamic compressive loading in articular chondrocytes. We first confirmed the presence of physically induced, TRPV4-dependent intracellular Ca(2+) signaling in agarose-embedded chondrocytes, and then used this model system to study the role of TRPV4 in regulating the response of chondrocytes to dynamic compression. Inhibition of TRPV4 during dynamic loading prevented acute, mechanically mediated regulation of proanabolic and anticatabolic genes, and furthermore, blocked the loading-induced enhancement of matrix accumulation and mechanical properties. Furthermore, chemical activation of TRPV4 by the agonist GSK1016790A in the absence of mechanical loading similarly enhanced anabolic and suppressed catabolic gene expression, and potently increased matrix biosynthesis and construct mechanical properties. These findings support the hypothesis that TRPV4-mediated Ca(2+) signaling plays a central role in the transduction of mechanical signals to support cartilage extracellular matrix maintenance and joint health. Moreover, these insights raise the possibility of therapeutically targeting TRPV4-mediated mechanotransduction for the treatment of diseases such as osteoarthritis, as well as to enhance matrix formation and functional properties of tissue-engineered cartilage as an alternative to bioreactor-based mechanical stimulation.
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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.