Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.
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.
Type
Journal articleSubject
Piezocartilage
cartilage injury
chondrocyte
mechanotransduction
Animals
Calcium Signaling
Cartilage, Articular
Chondrocytes
Ion Channels
Mice
RNA, Small Interfering
Stress, Mechanical
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https://hdl.handle.net/10161/12971Published Version (Please cite this version)
10.1073/pnas.1414298111Publication Info
Lee, Whasil; Leddy, Holly A; Chen, Yong; Lee, Suk Hee; Zelenski, Nicole A; McNulty,
Amy L; ... Liedtke, Wolfgang B (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 https://hdl.handle.net/10161/12971.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yong Chen
Associate Professor in Neurology
Jorg Grandl
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.
Farshid Guilak
Lazlo Ormandy Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Holly Leddy
Research & Dev Engineer III
Wolfgang Bernhard Liedtke
Adjunct Professor in the Department 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.
Amy Lynn McNulty
Associate Professor in Orthopaedic Surgery
The McNulty Lab is working to develop strategies to prevent osteoarthritis and to
promote tissue repair and regeneration following joint injury. In order to accomplish
this, we are working in three main areas. 1) We are working to understand the pathways
that are activated by normal and injurious mechanical loading of cartilage and meniscus
and how these mechanotransduction pathways are altered during aging, injury, and tissue
degeneration. A greater understanding of alterations in mech
Stefan Zauscher
Professor in the Department of Mechanical Engineering and 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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