Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage
Year: 2014
Type: article
Abstract: Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca(2+) signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca(2+) transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: State University of New York, National Institutes of Health, University of North Carolina at Chapel Hill, University at Buffalo, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Institute of Dental and Craniofacial Research
Awards: G1065035108, Computer Integrated Systems for Microscopy and Manipulation (CISMM), G1296071526, G1336186641, Engineering cartilage mechanotransduction for treatment of chondrocyte injury, G2189290587, G2434753226, G3126635433, Biomechanics and Inflammation in Osteoarthritis, G3851968304, Basic predoctoral training in neuroscience, Obesity, Biomechanics, and Inflammation in Osteoarthritis, G5256969710, Intrinsic Repair of the Knee Meniscus, Mechanosensitive ion channels and cortical mechanics, Viscoelastic Properties of Normal and OA Chondrons, G7078280491, Role of trpv4 in trigeminally mediated nociception, Mechanical and Osmotic Signaling in Chondrocytes, G9000024620
OpenAlex ID: W2027880075