Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model.
Abstract: Synovitis (SI) is one of the most common and serious orthopedic diseases in horses of different age, breed and sex, which contributes to the development of osteoarthritis. The burden of SI includes economic loss and represents a real challenge for current veterinary health care. At the molecular level, fibroblasts-like synoviocytes (FLS) are recognized as major cell populations involved in SI pathogenesis. In the course of SI, FLSs are losing their protective and pro-regenerative cytological features, become highly proliferative and initiate various stress signaling pathways. Fibroblast-like synoviocytes were treated with LPS in order to generate SI in vitro model. Mitochondria were isolated from peripheral blood derived mononuclear cells and co-cultured with FLS. After 24 h of culture, cells were subjected to RT-qPCR, western blot, cytometric and confocal microscopy analysis. Mitochondrial transfer (MT) was observed in vitro studies using confocal microscopy. Further studies revealed, that MT to LPS-treated FLS reduced cell proliferation, modulated apoptosis and decreased inflammatory response. Overall, MT Resulted in the considerable recovery of recipient cells cytophysiological properties. Presented data provides evidence that mitochondria transfersignificantly modulate FLS proliferative and metabolic activity through improved mitochondrial biogenesis and dynamics in activated FLS. Obtained results for the first time demonstrate that horizontal MT might be considered as a therapeutic tool for synovitis treatment; however, further clinical studies are strongly required. Video abstract.
© 2022. The Author(s).
Publication Date: 2022-09-07 PubMed ID: 36071528PubMed Central: PMC9450291DOI: 10.1186/s12964-022-00923-2Google Scholar: Lookup
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Summary
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The study explores the potential therapeutic impact of transferring mitochondria to fibroblasts-like synoviocytes (FLS) to restore their functionality in the case of synovitis (a common orthopedic disease in horses) induced in-vitro (lab conditions), demonstrating positive effects on cellular health and a reduction in inflammation.
Overview of the Problem
- Synovitis (SI) is a severe orthopedic issue commonly affecting horses. SI leads to significant economic losses and challenges for veterinary healthcare professional.
- Fibroblasts-like synoviocytes (FLS) are crucial cell groups linked to the SI’s pathology. When SI develops, these cells lose their cell-protective and pro-regenerative characteristics, become hyper-proliferative, and initiate stress signaling pathways.
Research Methodology
- To create a model of SI under lab conditions, FLS were exposed to Lipopolysaccharides (LPS).
- Mitochondria were derived from peripheral blood mononuclear cells and co-cultivated with FLS.
- Post a 24-hour culture period, the cells were analyzed using RT-qPCR, western blot, cytometry, and confocal microscopy. The transfer of mitochondria was visualized via confocal microscopy.
Key Findings
- The transfer of mitochondria to LPS-treated FLS was observed to reduce cell proliferation, modulate apoptosis (cell death), and diminish the inflammatory response.
- Overall, the transfer of mitochondria led to a significant recovery in the cytophysiological properties of the recipient cells.
- It was seen that the mitochodrial transfer greatly adjusted FLS’s proliferative and metabolic activity via improved mitochondrial biogenesis (growth and division of pre-existing mitochondria) and dynamics among activated FLS.
Conclusions and Future Directions
- The data serves as the first evidence demonstrating that horizontal mitochondrial transfer might be a potential treatment method for SI.
- However, the study suggests a necessity for more clinical trials to further validate the therapy.
Cite This Article
APA
Kornicka-Garbowska K, Groborz S, Lynda B, Galuppo L, Marycz K.
(2022).
Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model.
Cell Commun Signal, 20(1), 137.
https://doi.org/10.1186/s12964-022-00923-2 Publication
Researcher Affiliations
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 Building, 50-375, Wroclaw, Poland.
- International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
- International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 Building, 50-375, Wroclaw, Poland.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
- Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B Street, A7 Building, 50-375, Wroclaw, Poland. kmmarycz@ucdavis.edu.
- International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland. kmmarycz@ucdavis.edu.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. kmmarycz@ucdavis.edu.
MeSH Terms
- Animals
- Cells, Cultured
- Fibroblasts / metabolism
- Horses
- Lipopolysaccharides / pharmacology
- Mitochondria
- Synoviocytes / metabolism
- Synovitis / metabolism
Conflict of Interest Statement
The authors declare no competing interests.
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Citations
This article has been cited 2 times.- Kornicka-Garbowska K, Groborz S, Lynda B, Galuppo L, Marycz K. Correction: Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model.. Cell Commun Signal 2023 Jun 12;21(1):128.
- Jing W, Liu C, Su C, Liu L, Chen P, Li X, Zhang X, Yuan B, Wang H, Du X. Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.. Front Immunol 2023;14:1107670.
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