Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.
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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.
RNA, Small Interfering
Published Version (Please cite this version)10.1073/pnas.1414298111
Publication InfoBeicker, KN; Chen, Y; Coles, J; Grandl, J; Guilak, Farshid; Leddy, HA; ... Zelenski, NA (2014). Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc Natl Acad Sci U S A, 111(47). pp. E5114-E5122. 10.1073/pnas.1414298111. Retrieved from http://hdl.handle.net/10161/12971.
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Associate Professor of Neurobiology
Ion channels can be activated (gated) by various stimuli such as chemicals, voltage, pressure and temperature. We develop novel biophysical techniques to identify mechanisms of ion channel function.
Lazlo Ormandy Professor of Orthopaedic Surgery
Professor of Neurology
Research Interests in the Liedtke-Lab: Pain/ nociception Sensory transduction and -transmission TRP ion channels Water and salt equilibrium regulated by the central nervous system Visit the lab's website, download papers and read Dr. Liedtke's CV here.
Assistant Professor in Orthopaedic Surgery
The long term goals of the McNulty lab are to develop strategies to prevent osteoarthritis and to promote tissue repair and regeneration following joint injury. In order to achieve these goals, we need to understand the mechanisms necessary for tissue repair and regeneration and how they are altered with aging and joint injury. Specifically, we are working to enhance the integrative repair of meniscus to restore meniscal function and decrease the risk of osteoarthritis development. &
Sternberg Family Professor of Mechanical Engineering & Materials Science
My research lies at the intersection of surface and colloid science, polymer materials engineering, and biointerface science, with four central areas of focus: 1. Fabrication, manipulation and characterization of stimulus-responsive biomolecular and bio-inspired polymeric nanostructures on surfaces; 2. Nanotechnology of soft-wet materials and hybrid biological/non-biological microdevices; 3. Receptor-ligand interactions relevant to the diagnostics of infectious diseases; 4. Friction
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