The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models.
Abstract: Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage degradation, chronic inflammation, and progressive joint dysfunction. Despite rising incidences driven by ageing and increasing obesity, potent treatments remain elusive, exacerbating the socioeconomic burden. OA pathogenesis involves an imbalance in extracellular matrix (ECM) turnover, mediated by inflammatory cytokines and matrix-degrading enzymes, leading to oxidative stress, chondrocyte apoptosis, and ECM degradation. Additionally, synovial inflammation (synovitis) plays a critical role in disease progression through molecular crosstalk with cartilage and other joint tissues. Existing and OA models face significant limitations in replicating human pathophysiology, particularly the complex interplay between joint tissues. Equine models, due to their anatomical and cellular similarities to humans, offer translational relevance but remain underutilized. This study aims to develop an advanced 3D coculture system using equine chondrocytes and synoviocytes to simulate tissue-level interactions and fluid mechanical forces involved in OA. By incorporating inflammatory stimuli and gravity-driven cyclic fluid actuation, this model enables the study of OA-related molecular interactions in both healthy and diseased conditions under dynamic fluid conditions. Findings from this research provide important insights into pathological tissue crosstalk. In turn, this can help to better understand underlying inflammatory pathways and the potential contribution of fluid flow as an influential factor on the tissue microenvironment.
Publication Date: 2025-03-31 PubMed ID: 40162708DOI: 10.1039/d4lc01078gGoogle Scholar: Lookup
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The research article discusses a study aimed at developing an advanced 3D coculture system using equine cells to simulate tissue-level interactions and fluid mechanical forces involved in Osteoarthritis (OA), a prevalent degenerative joint disorder.
Understanding Osteoarthritis
- Osteoarthritis is a degenerative joint disorder, primarily characterized by the degradation of cartilage, chronic inflammation, and progressive joint dysfunction. The occurrence of OA has been increasing due to factors like aging and obesity, leading to a substantial socioeconomic burden.
- The pathogenesis, or the mechanism leading to the development of OA, involves an imbalance in the turnover of the extracellular matrix (ECM). This is mediated by inflammatory cytokines and matrix-degrading enzymes, causing oxidative stress, apoptosis or programmed cell death of the chondrocytes (cells in the cartilage), and further degradation of the ECM.
- Additionally, inflammation of the synovial tissue, a condition called synovitis, plays a critical role in the progression of OA. The molecular crosstalk between cartilage and other joint tissues aggravates the disease state.
- Existing models face limitations in replicating human pathophysiology, especially the complex interaction between different joint tissues.
Employing Equine Models
- However, utilizing equine models, which have anatomical and cellular similarities with humans, can provide better translational relevance in studying OA.
- The research aims to develop an advanced 3D coculture system that uses both equine chondrocytes and synoviocytes (cells found in the synovial fluid). This model is designed to simulate the tissue-level interactions and fluid mechanical forces associated with OA.
- The model integrates inflammatory stimuli and cyclic fluid actuation driven by gravity. This provision allows the study of OA-related molecular interactions in both healthy and diseased conditions under dynamic fluid conditions.
Significance of Research Findings
- The findings from this research offer important insights into pathological tissue crosstalk in OA, a crucial aspect of the disease progression.
- The understanding of these underlying inflammatory pathways, and the potential influence of fluid flow on the tissue microenvironment, can pave the way for developing effective interventions and treatments for OA.
Cite This Article
APA
Heidenberger J, Reihs EI, Strauss J, Frauenlob M, Gültekin S, Gerner I, Tögel S, Ertl P, Windhager R, Jenner F, Rothbauer M.
(2025).
The effect of cyclic fluid perfusion on the proinflammatory tissue environment in osteoarthritis using equine joint-on-a-chip models.
Lab Chip.
https://doi.org/10.1039/d4lc01078g Publication
Researcher Affiliations
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Faculty of Technical Chemistry, Technische Universität Wien, Getreidemarkt 9/163, 1060 Vienna, Austria. mario.rothbauer@tuwien.ac.at.
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Faculty of Technical Chemistry, Technische Universität Wien, Getreidemarkt 9/163, 1060 Vienna, Austria. mario.rothbauer@tuwien.ac.at.
- Faculty of Technical Chemistry, Technische Universität Wien, Getreidemarkt 9/163, 1060 Vienna, Austria. mario.rothbauer@tuwien.ac.at.
- Department for Small Animals and Horses, Centre for Equine Health and Research, Equine Surgery Unit, Veterinary Regenerative Medicine Laboratory, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
- Department for Small Animals and Horses, Centre for Equine Health and Research, Equine Surgery Unit, Veterinary Regenerative Medicine Laboratory, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria.
- Faculty of Technical Chemistry, Technische Universität Wien, Getreidemarkt 9/163, 1060 Vienna, Austria. mario.rothbauer@tuwien.ac.at.
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Department for Small Animals and Horses, Centre for Equine Health and Research, Equine Surgery Unit, Veterinary Regenerative Medicine Laboratory, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
- Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. mario.rothbauer@muv.ac.at.
- Faculty of Technical Chemistry, Technische Universität Wien, Getreidemarkt 9/163, 1060 Vienna, Austria. mario.rothbauer@tuwien.ac.at.
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