The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes
Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing to the overall chronic nature of desmopathy. A major challenge has been the lack of representative two-dimensional (2D) in vitro models mimi...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1469238/full |
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| author | Johannes Heidenberger Raphael Hangel Eva I. Reihs Eva I. Reihs Jonathan Strauss Jonathan Strauss Petra Liskova Jürgen Alphonsus Jürgen Alphonsus Cornelia Brunner Kevin Döring Iris Gerner Florien Jenner Reinhard Windhager Stefan Toegel Stefan Toegel Mario Rothbauer Mario Rothbauer Mario Rothbauer |
| author_facet | Johannes Heidenberger Raphael Hangel Eva I. Reihs Eva I. Reihs Jonathan Strauss Jonathan Strauss Petra Liskova Jürgen Alphonsus Jürgen Alphonsus Cornelia Brunner Kevin Döring Iris Gerner Florien Jenner Reinhard Windhager Stefan Toegel Stefan Toegel Mario Rothbauer Mario Rothbauer Mario Rothbauer |
| author_sort | Johannes Heidenberger |
| collection | DOAJ |
| description | Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing to the overall chronic nature of desmopathy. A major challenge has been the lack of representative two-dimensional (2D) in vitro models mimicking inflammatory processes in the presence of dynamic mechanical strain, both being crucial for ligament homeostasis. Physiological levels of strain exert anti-inflammatory effects, while excessive strain can facilitate inflammatory mechanisms. Adhering to the 3Rs (Replacement, Reduction and Refinement) principles of animal research, this study aims to investigate the role of a dynamic biomechanical in vitro environment on inflammatory mechanisms by combining a Flexcell culture system with primary human ligamentocytes for the study of ligament pathology. Primary ligamentocytes from OA patients were cultured under animal-free conditions with human platelet lysate, and exposed to either IL-1β or TGF-β3 to simulate different inflammatory microenvironments. Cells were subjected to different magnitudes of mechanical strain. Results showed that cells aligned along the force axis under strain. This study highlights the critical role of the mechanical microenvironment in modulating inflammatory and fibrotic cellular responses in ligamentocyte pathology, providing valuable insights into the complex interplay between biomechanical stimuli and cytokine signaling. These findings not only advance our understanding of ligament biology but also can pave the way for the development of more targeted therapeutic strategies for ligament injuries and diseases, potentially improving patient outcomes in orthopedic medicine. |
| format | Article |
| id | doaj-art-a29ef602c57245d2a9b2017c5aa122bc |
| institution | OA Journals |
| issn | 2296-4185 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-a29ef602c57245d2a9b2017c5aa122bc2025-08-20T01:59:21ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-12-011210.3389/fbioe.2024.14692381469238The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytesJohannes Heidenberger0Raphael Hangel1Eva I. Reihs2Eva I. Reihs3Jonathan Strauss4Jonathan Strauss5Petra Liskova6Jürgen Alphonsus7Jürgen Alphonsus8Cornelia Brunner9Kevin Döring10Iris Gerner11Florien Jenner12Reinhard Windhager13Stefan Toegel14Stefan Toegel15Mario Rothbauer16Mario Rothbauer17Mario Rothbauer18Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaInstitute of Applied Synthetic Chemistry, Faculty of Technical Chemistry, Technische Universitaet Wien, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaInstitute of Applied Synthetic Chemistry, Faculty of Technical Chemistry, Technische Universitaet Wien, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaDivision of Orthopedics, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaDivision of Orthopedics, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaVeterinary Tissue Engineering and Regenerative Medicine Vienna (VETERM), Equine Surgery Unit, University of Veterinary Medicine Vienna, Vienna, AustriaVeterinary Tissue Engineering and Regenerative Medicine Vienna (VETERM), Equine Surgery Unit, University of Veterinary Medicine Vienna, Vienna, AustriaDivision of Orthopedics, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaLudwig Boltzmann Institute of Arthritis and Rehabilitation, Vienna, AustriaKarl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, AustriaInstitute of Applied Synthetic Chemistry, Faculty of Technical Chemistry, Technische Universitaet Wien, Vienna, AustriaLudwig Boltzmann Institute of Arthritis and Rehabilitation, Vienna, AustriaBiomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing to the overall chronic nature of desmopathy. A major challenge has been the lack of representative two-dimensional (2D) in vitro models mimicking inflammatory processes in the presence of dynamic mechanical strain, both being crucial for ligament homeostasis. Physiological levels of strain exert anti-inflammatory effects, while excessive strain can facilitate inflammatory mechanisms. Adhering to the 3Rs (Replacement, Reduction and Refinement) principles of animal research, this study aims to investigate the role of a dynamic biomechanical in vitro environment on inflammatory mechanisms by combining a Flexcell culture system with primary human ligamentocytes for the study of ligament pathology. Primary ligamentocytes from OA patients were cultured under animal-free conditions with human platelet lysate, and exposed to either IL-1β or TGF-β3 to simulate different inflammatory microenvironments. Cells were subjected to different magnitudes of mechanical strain. Results showed that cells aligned along the force axis under strain. This study highlights the critical role of the mechanical microenvironment in modulating inflammatory and fibrotic cellular responses in ligamentocyte pathology, providing valuable insights into the complex interplay between biomechanical stimuli and cytokine signaling. These findings not only advance our understanding of ligament biology but also can pave the way for the development of more targeted therapeutic strategies for ligament injuries and diseases, potentially improving patient outcomes in orthopedic medicine.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1469238/fullmechanical loadingligamentocytesinflammationfibrosisin vitro modelling |
| spellingShingle | Johannes Heidenberger Raphael Hangel Eva I. Reihs Eva I. Reihs Jonathan Strauss Jonathan Strauss Petra Liskova Jürgen Alphonsus Jürgen Alphonsus Cornelia Brunner Kevin Döring Iris Gerner Florien Jenner Reinhard Windhager Stefan Toegel Stefan Toegel Mario Rothbauer Mario Rothbauer Mario Rothbauer The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes Frontiers in Bioengineering and Biotechnology mechanical loading ligamentocytes inflammation fibrosis in vitro modelling |
| title | The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes |
| title_full | The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes |
| title_fullStr | The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes |
| title_full_unstemmed | The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes |
| title_short | The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes |
| title_sort | modulating role of uniaxial straining in the il 1β and tgf β mediated inflammatory response of human primary ligamentocytes |
| topic | mechanical loading ligamentocytes inflammation fibrosis in vitro modelling |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2024.1469238/full |
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