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

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Lee, Whasil

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Leddy, Holly A

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Chen, Yong

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Lee, Suk Hee

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Zelenski, Nicole A

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McNulty, Amy L

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Wu, Jason

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Beicker, Kellie N

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Coles, Jeffrey

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Zauscher, Stefan

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Grandl, Jörg

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Sachs, Frederick

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Guilak, Farshid

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Liedtke, Wolfgang B

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United States

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2016-10-21T03:00:37Z

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2014-11-25

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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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/25385580

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1414298111

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1091-6490

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https://hdl.handle.net/10161/12971

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eng

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Proceedings of the National Academy of Sciences

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Proc Natl Acad Sci U S A

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10.1073/pnas.1414298111

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Piezo

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cartilage

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cartilage injury

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chondrocyte

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mechanotransduction

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Animals

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Calcium Signaling

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Cartilage, Articular

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Chondrocytes

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Ion Channels

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Mice

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RNA, Small Interfering

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Stress, Mechanical

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

dc.type

Journal article

duke.contributor.orcid

McNulty, Amy L|0000-0003-0556-0106

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Zauscher, Stefan|0000-0002-2290-7178

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Grandl, Jörg|0000-0001-7179-7609

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Liedtke, Wolfgang B|0000-0003-4166-5394

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/25385580

pubs.begin-page

E5114

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E5122

pubs.issue

47

pubs.organisational-group

Anesthesiology

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Basic Science Departments

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Biomedical Engineering

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Chemistry

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Clinical Science Departments

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Duke

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Duke Institute for Brain Sciences

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Institutes and Provost's Academic Units

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Mechanical Engineering and Materials Science

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Neurobiology

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Neurology

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Neurology, Headache and Pain

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Orthopaedics

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Pathology

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Pratt School of Engineering

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School of Medicine

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Trinity College of Arts & Sciences

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University Institutes and Centers

pubs.publication-status

Published

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111

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