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  11. The Chondrocyte "mechanome": Activation Of The Mechanosensitive Ion Channels Trpv4 And Piezo1 Drives Unique Transcriptional Signatures

The chondrocyte "mechanome": Activation of the mechanosensitive ion channels TRPV4 and PIEZO1 drives unique transcriptional signatures

Robert Nims1,2,3, Daniel R Palmer1,2,3,4, Jordan Kassab4

  • 1Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 3, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Mechanosensitive ion channels TRPV4 and PIEZO1 activate distinct gene expression in chondrocytes. PIEZO1 activation can promote cartilage health or inflammation, offering therapeutic targets for osteoarthritis.

Area of Science:

  • Cell Biology
  • Mechanobiology
  • Molecular Biology

Background:

  • Mechanosensitive ion channels, including Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1, are crucial for chondrocyte function.
  • TRPV4 activation promotes chondrogenesis, while PIEZO1 activation under supraphysiologic stress can lead to cell death.
  • The distinct transcriptomic responses and functional consequences of TRPV4 and PIEZO1 activation remain largely uncharacterized.

Purpose of the Study:

  • To comprehensively investigate and contrast the transcriptomic responses to TRPV4 and PIEZO1 activation in chondrocytes.
  • To correlate these transcriptomes with specific cellular functions and behaviors.
  • To identify unique and shared gene expression patterns influenced by these mechanosensitive channels.

Main Methods:

Keywords:
inflammationmechanobiologymechanotransductionosteoarthritis

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  • RNA sequencing was employed to analyze the transcriptomes of chondrocytes upon activation of TRPV4 and PIEZO1.
  • Comparative analysis of gene expression profiles was performed.
  • Functional assessments, including sulfated glycosaminoglycan deposition, were conducted.

    • Main Results:

    • TRPV4 and PIEZO1 activation result in distinct transcriptomes with unique co-regulated gene clusters.
    • PIEZO1 activation under supraphysiologic deformation induced a transient inflammatory profile associated with cartilage degradation and osteoarthritis.
    • Both channels demonstrated anabolic effects, with PIEZO1 promoting a pro-chondrogenic transcriptome and increasing glycosaminoglycan deposition in vitro.

    Conclusions:

    • Chondrocytes possess a broad "mechanome" where TRPV4 and PIEZO1 activation elicit discrete cellular responses.
    • PIEZO1 plays complex roles in both physiologic and pathologic chondrocyte functions, potentially influencing osteoarthritis progression.
    • Understanding these distinct transcriptomic profiles can guide the development of novel therapeutics targeting mechanosensitive channels for osteoarthritis management.
    transcriptomics