Galvanic current activates the NLRP3 inflammasome to promote type I collagen production in tendon

Abstract

The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 to 7.

Article and author information

Author details

  1. Alejandro Peñin-Franch

    Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
    Competing interests
    Alejandro Peñin-Franch, PhD contract was supported by MVClinic Institute and Prim.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5329-1671
  2. José Antonio García-Vidal

    University of Murcia, Murcia, Spain
    Competing interests
    No competing interests declared.
  3. Carlos M Martínez

    Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3307-1326
  4. Pilar Escolar-Reina

    University of Murcia, Murcia, Spain
    Competing interests
    No competing interests declared.
  5. Rosa M Martínez-Ojeda

    University of Murcia, Murcia, Spain
    Competing interests
    No competing interests declared.
  6. Ana Isabel Gómez

    Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
    Competing interests
    No competing interests declared.
  7. Juan M Bueno

    University of Murcia, Murcia, Spain
    Competing interests
    No competing interests declared.
  8. Francisco Minaya-Muñoz

    MV Clinic, Madrid, Spain
    Competing interests
    Francisco Minaya-Muñoz, Employe of MVClinic Institute.
  9. Fermín Valera-Garrido

    MV Clinic, Madrid, Spain
    Competing interests
    Fermín Valera-Garrido, Employe of MVClinic Institute.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8867-2519
  10. Francesc Medina-Mirapeix

    University of Murcia, Murcia, Spain
    Competing interests
    No competing interests declared.
  11. Pablo Pelegrín

    University of Murcia, Murcia, Spain
    For correspondence
    pablo.pelegrin@imib.es
    Competing interests
    Pablo Pelegrín, Inventor in a patent filed on March 2020 by the Fundación para la Formación e Investigación Sanitaria de la Región de Murcia (PCT/EP2020/056729) for a method to identify NLRP3-immunocompromised sepsis patients. Is consultant of Glenmark Pharmaceutical and co-founder of Viva in vitro diagnostics SL..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9688-1804

Funding

Ministerio de Ciencia, Innovación y Universidades (SAF2017‐88276‐R)

  • Pablo Pelegrín

Ministerio de Ciencia, Innovación y Universidades (PID2020-116709RB-I00)

  • Pablo Pelegrín

Fundación Séneca (20859/PI/18)

  • Pablo Pelegrín

Fundación Séneca (21081/PDC/19)

  • Pablo Pelegrín

European Research Council (614578)

  • Pablo Pelegrín

European Research Concil (899636)

  • Pablo Pelegrín

Ministerio de Ciencia, Innovación y Universidades (PID2020-113919RB-I00)

  • Juan M Bueno

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental protocols for animal handling were refined and approved by the local animal research ethical committee (references 241/2016 and 541/2019) and Animal Health Service of the General Directorate of Fishing and Farming of the Council of Murcia (Servicio de Sanidad Animal, Dirección General de Ganadería y Pesca, Consejería de Agricultura y Agua de la Región de Murcia, reference A13160702). Animal experimentation was performed in strict accordance with the Hospital Clínico Universitario Vírgen de la Arrixaca animal experimentation guidelines, and the Spanish national (RD 1201/2005 and Law 32/2007) and EU (86/609/EEC and 2010/63/EU) legislation.

Human subjects: We present non-invasive ultrasound scanning images from routinely clinical following from a single patient. The data is completely anonymised and from the normal clinical routine practice.

Reviewing Editor

  1. Yousef Abu-Amer, Washington University School of Medicine, United States

Publication history

  1. Received: September 7, 2021
  2. Preprint posted: September 22, 2021 (view preprint)
  3. Accepted: February 23, 2022
  4. Accepted Manuscript published: February 24, 2022 (version 1)
  5. Version of Record published: March 4, 2022 (version 2)

Copyright

© 2022, Peñin-Franch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alejandro Peñin-Franch
  2. José Antonio García-Vidal
  3. Carlos M Martínez
  4. Pilar Escolar-Reina
  5. Rosa M Martínez-Ojeda
  6. Ana Isabel Gómez
  7. Juan M Bueno
  8. Francisco Minaya-Muñoz
  9. Fermín Valera-Garrido
  10. Francesc Medina-Mirapeix
  11. Pablo Pelegrín
(2022)
Galvanic current activates the NLRP3 inflammasome to promote type I collagen production in tendon
eLife 11:e73675.
https://doi.org/10.7554/eLife.73675

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