ArticleThe Journal of biological chemistry
Mechanotransduction via a TRPV4-Rac1 signaling axis plays a role in multinucleated giant cell formation.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- A novel role for TRPV1 in macrophage giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- A Novel Core-Shell Hydrogel 3D Model for Studying Macrophage Mechanosensing and Foreign Body Giant Cell Formation.Advanced healthcare materials · 2026Article
- TRPV4-Mediated Mechanosensing Regulates the Endothelial-to-Mesenchymal Transition: Implications for Atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Osteopontin attenuates the foreign-body response to silicone implants.Nature biomedical engineering · 2025Article
- Macrophage Polarization Profiling in Dynamic Culture System.Cellular and molecular bioengineering · 2025Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants.Biomaterials · 2025Article
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Avocado-derived extracellular vesicles loaded with ginkgetin and berberine prevent inflammation and macrophage foam cell formation.Journal of cellular and molecular medicine · 2024Article
- Macrophages and fibroblasts in foreign body reactions: How mechanical cues drive cell functions?Materials today. Bio · 2023Review
- Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation.Bone reports · 2023Article
- Mechanical strain stimulates COPII-dependent secretory trafficking via Rac1.The EMBO journal · 2022Article
- Role of mechanosensitive channels/receptors in atherosclerosis.American journal of physiology. Cell physiology · 2022Review
- The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing.Journal of inflammation research · 2022Review
- Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.Science signaling · 2021Article
- Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction.Cells · 2021Review
- Mechanosensitive Regulation of Fibrosis.Cells · 2021Review
- Diverse Roles of TRPV4 in Macrophages: A Need for Unbiased Profiling.Frontiers in immunology · 2021Review
- Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multinucleated giant cells are formed by the fusion of macrophages and are a characteristic feature in numerous pathophysiological conditions including the foreign body response (FBR). Foreign body giant cells (FBGCs) are inflammatory and destructive multinucleated macrophages and may cause damage and/or rejection of implants. However, while these features of FBGCs are well established, the molecular mechanisms underlying their formation remain elusive. Improved understanding of the molecular mechanisms underlying the formation of FBGCs may permit the development of novel implants that eliminate or reduce the FBR. Our previous study showed that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel/receptor, is required for FBGC formation and FBR to biomaterials. Here, we have determined that (a) TRPV4 is directly involved in fusogenic cytokine (interleukin-4 plus granulocyte macrophage-colony stimulating factor)-induced activation of Rac1, in bone marrow-derived macrophages; (b) TRPV4 directly interacts with Rac1, and their interaction is further augmented in the presence of fusogenic cytokines; (c) TRPV4-dependent activation of Rac1 is essential for the augmentation of intracellular stiffness and regulation of cytoskeletal remodeling; and (d) TRPV4-Rac1 signaling axis is critical in fusogenic cytokine-induced FBGC formation. Together, these data suggest a novel mechanism whereby a functional interaction between TRPV4 and Rac1 leads to cytoskeletal remodeling and intracellular stiffness generation to modulate FBGC formation.
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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.