ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 169 citations in OpenAlex.
- The F-Actin of In Situ Chondrocytes in Non-Degenerate and Mildly-Degenerate Human Cartilage: Changes With Cell Volume, and Cytoplasmic Processes.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Exercise-primed Trpv4+ progenitors sense mechanical to regulate graded transition in enthesis regeneration.Bone & joint research · 2026Article
- 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
- Role of collagen VI and IX in mechanotransduction in the cartilage microenvironments: A multiscale in silico examination.Journal of orthopaedic translation · 2026Article
- The notochord: development, disease and stem cell-based modelling.Development (Cambridge, England) · 2026Review
- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- Early Post‑Traumatic Osteoarthritis Features Greater Cartilage Extracellular Matrix Proteoglycan Loss Compared to the Pericellular Matrix.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Viscoelastic recovery time of chondrocytes from monolayer and alginate cultures.bioRxiv : the preprint server for biology · 2026Article
- A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells.Stem cell research & therapy · 2026Article
- Tissue and extracellular matrix remodeling of the subchondral bone during osteoarthritis of knee joints as revealed by spatial mass spectrometry imaging.Bone research · 2026Article
- Visualization and Organization of Collagen VI Containing Suprastructures in Articular Cartilage.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Article
- Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Development of the mechanoresponsive pericellular matrix of chondrons.Science advances · 2025Article
- Fibrocartilage hyalinization: A potential therapeutic strategy for articular fibrocartilage.Journal of orthopaedic translation · 2025Review
- Restoring articular cartilage: insights from structure, composition and development.Nature reviews. Rheumatology · 2025Review
- Decellularized Extracellular Matrix Improves Mesenchymal Stromal Cell Spheroid Response to Chondrogenic Stimuli.Tissue engineering. Part A · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveMechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties.
methodsConfocal laser scanning microscopy was used to image TRPV4-mediated calcium signaling and osmotically induced cell swelling in intact femora from 2- and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1(-/-)) mice. Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan.
resultsHypo-osmotic stress-induced TRPV4-mediated calcium signaling was increased in Col6a1(-/-) mice relative to WT controls at 2 months. Col6a1(-/-) mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages.
conclusionIn contrast to our original hypothesis, type VI collagen was not required for TRPV4-mediated Ca(2+) signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age-dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels.
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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.