Purinergic receptors play a key role in shock wave-induced proliferation

Abstract Shock wave treatment (SWT) is a non-invasive therapy applied in musculoskeletal and urological disorders, as well as in chronic wound regeneration. As the use of medical SWT broadens, it is important to better understand the molecular mechanisms underlying its success. Here, we identified P...

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Main Authors: Dorota Szwarc-Hofbauer, Elisabeth Simböck, Carina Hromada, Michaela Stoiber, Janine Tomasch, Georg Weitzer, Andreas Teuschl-Woller
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-02955-3
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author Dorota Szwarc-Hofbauer
Elisabeth Simböck
Carina Hromada
Michaela Stoiber
Janine Tomasch
Georg Weitzer
Andreas Teuschl-Woller
author_facet Dorota Szwarc-Hofbauer
Elisabeth Simböck
Carina Hromada
Michaela Stoiber
Janine Tomasch
Georg Weitzer
Andreas Teuschl-Woller
author_sort Dorota Szwarc-Hofbauer
collection DOAJ
description Abstract Shock wave treatment (SWT) is a non-invasive therapy applied in musculoskeletal and urological disorders, as well as in chronic wound regeneration. As the use of medical SWT broadens, it is important to better understand the molecular mechanisms underlying its success. Here, we identified P2X4 and P2Y2 purinergic receptors to be primarily expressed in C3H/10T1/2 mouse mesenchymal stromal cells and investigated their role in the initiation of the signaling events following SWT using single- and double-receptor knock-out (KO) cell lines. We show that SWT induced the expression of c-Jun and c-Fos within 30 min after stimulation and that the SWT-induced Erk1/2 pathway activation and immediate early gene expression were decreased in P2Y2-, P2X4- and P2Y2/P2X4-deficient cells. Importantly, SWT did not promote proliferation in P2Y2/P2X4-deficient cells, while loss of either one of the receptors significantly reduced the proliferative effect, indicating a cumulative effect of their loss. Finally, our data suggests a more prominent role of the P2Y2 receptor in SWT-induced cellular effects, since primarily its loss contributed to the observed changes. With these findings, we further the understanding of the molecular mechanisms of SWT and propose that the varying expression of purinergic receptors in tissues should be considered when establishing treatment protocols.
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spelling doaj-art-92dc38ce97844a3596dcdb2fea44c4ba2025-08-20T03:16:40ZengNature PortfolioScientific Reports2045-23222025-05-0115111710.1038/s41598-025-02955-3Purinergic receptors play a key role in shock wave-induced proliferationDorota Szwarc-Hofbauer0Elisabeth Simböck1Carina Hromada2Michaela Stoiber3Janine Tomasch4Georg Weitzer5Andreas Teuschl-Woller6Department Life Science Engineering, University of Applied Sciences Technikum WienDepartment Life Science Engineering, University of Applied Sciences Technikum WienDepartment Life Science Engineering, University of Applied Sciences Technikum WienDepartment Life Science Engineering, University of Applied Sciences Technikum WienDepartment Life Science Engineering, University of Applied Sciences Technikum WienMax Perutz Labs, Vienna Biocenter Campus (VBC)Department Life Science Engineering, University of Applied Sciences Technikum WienAbstract Shock wave treatment (SWT) is a non-invasive therapy applied in musculoskeletal and urological disorders, as well as in chronic wound regeneration. As the use of medical SWT broadens, it is important to better understand the molecular mechanisms underlying its success. Here, we identified P2X4 and P2Y2 purinergic receptors to be primarily expressed in C3H/10T1/2 mouse mesenchymal stromal cells and investigated their role in the initiation of the signaling events following SWT using single- and double-receptor knock-out (KO) cell lines. We show that SWT induced the expression of c-Jun and c-Fos within 30 min after stimulation and that the SWT-induced Erk1/2 pathway activation and immediate early gene expression were decreased in P2Y2-, P2X4- and P2Y2/P2X4-deficient cells. Importantly, SWT did not promote proliferation in P2Y2/P2X4-deficient cells, while loss of either one of the receptors significantly reduced the proliferative effect, indicating a cumulative effect of their loss. Finally, our data suggests a more prominent role of the P2Y2 receptor in SWT-induced cellular effects, since primarily its loss contributed to the observed changes. With these findings, we further the understanding of the molecular mechanisms of SWT and propose that the varying expression of purinergic receptors in tissues should be considered when establishing treatment protocols.https://doi.org/10.1038/s41598-025-02955-3
spellingShingle Dorota Szwarc-Hofbauer
Elisabeth Simböck
Carina Hromada
Michaela Stoiber
Janine Tomasch
Georg Weitzer
Andreas Teuschl-Woller
Purinergic receptors play a key role in shock wave-induced proliferation
Scientific Reports
title Purinergic receptors play a key role in shock wave-induced proliferation
title_full Purinergic receptors play a key role in shock wave-induced proliferation
title_fullStr Purinergic receptors play a key role in shock wave-induced proliferation
title_full_unstemmed Purinergic receptors play a key role in shock wave-induced proliferation
title_short Purinergic receptors play a key role in shock wave-induced proliferation
title_sort purinergic receptors play a key role in shock wave induced proliferation
url https://doi.org/10.1038/s41598-025-02955-3
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