title: Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes.
abstract: The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively. Both TRPV4 and PIEZO1 channels contribute to currents activated by stimuli applied at cell-substrate contacts but only PIEZO1 mediates stretch-activated currents. These data demonstrate that there are separate, but overlapping, mechanoelectrical transduction pathways in chondrocytes.
authors.affiliation: Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Martha Rocio
authors.initials: MR
authors.lastname: Servin-Vences
authors.affiliation: Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Moroni
authors.affiliation: Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Gary R
authors.identifier: 0000-0002-2890-6352
authors.initials: GR
authors.lastname: Lewin
authors.affiliation: Department of Neuroscience, Max Delbruck Center for Molecular Medicine, Berlin, Germany.|Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia.|EMBL Australia node for Single Molecule Sciences, School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Kate
authors.identifier: 0000-0003-0879-6093
authors.initials: K
authors.lastname: Poole
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D003584:Cytological Techniques; D007473:Ion Channels / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D007473:Ion Channels; C552920:Piezo1 protein, mouse; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse
keywords: PIEZO1; TRPV4; biophysics; cell biology; chondrocytes; mechanoelectrical transduction; mouse; structural biology