Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Thumbnail
View / Download
1.4 Mb
Date
2014-11-25
Authors
Lee, Whasil
Leddy, Holly A
Chen, Yong
Lee, Suk Hee
Zelenski, Nicole A
McNulty, Amy L
Wu, Jason
Beicker, Kellie N
Coles, Jeffrey
Zauscher, Stefan
Grandl, Jörg
Sachs, Frederick
Guilak, Farshid
Liedtke, Wolfgang B
Show More
(14 total)
Repository Usage Stats
211
views
154
downloads
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 article
Subject
Piezo
cartilage
cartilage injury
chondrocyte
mechanotransduction
Animals
Calcium Signaling
Cartilage, Articular
Chondrocytes
Ion Channels
Mice
RNA, Small Interfering
Stress, Mechanical
Permalink
https://hdl.handle.net/10161/12971
Published Version (Please cite this version)
10.1073/pnas.1414298111
Publication 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.
Collections
  • Scholarly Articles
More Info
Show full item record

Scholars@Duke

Chen

Yong Chen

Associate Professor in Neurology
Grandl

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.
Leddy

Holly Leddy

Research & Dev Engineer III
Liedtke

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.
McNulty

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
Zauscher

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
More Authors
Alphabetical list of authors with Scholars@Duke profiles.
Open Access

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

Rights for Collection: Scholarly Articles


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University