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Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model.
Abstract: Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2- production. To identify the underlying molecular actors, stable isotope-labeling by amino acids in cell culture based secreted protein analyses were conducted, in the presence of serum. The relative abundance of highly sequenced proteins was finally confirmed by western blot. Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses. These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.
© 2022. The Author(s).
Publication Date: 2022-10-22 PubMed ID: 36271312PubMed Central: PMC9902419DOI: 10.1007/s12015-022-10463-4Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Cell Culture
- Cytokines
- Degenerative Joint Disease
- Equine Diseases
- Equine Health
- Equine model
- Experimental Methods
- Extracellular matrix
- Glycosaminoglycan
- In Vitro Research
- Inflammation
- Interleukins
- Mesenchymal Cells
- Osteoarthritis
- Proteomics
- Tumor Necrosis Factor
- Veterinary Care
- Veterinary Medicine
- Veterinary Research
- Western Blot
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The study analyses muscle-derived mesenchymal stem cells (mdMSCs) and their potential use in treating osteoarthritis, a common joint degenerative disease. The researchers used a model of osteoarthritis and found that mdMSCs decrease the induced glycosaminoglycan release and show certain molecular activities which could support their use in cell therapy for osteoarthritis.
Osteoarthritis and the Role of Mesenchymal Stem Cells
- The research aimed to explore the potential of mesenchymal stem cells, particularly those derived from muscle (mdMSCs), in treating osteoarthritis, a degenerative joint disease prevalent in humans and horses.
- The authors started with the development of an equine osteoarthritis model using cartilage explants exposed to pro-inflammatory cytokines.
- Mesenchymal stem cells are seen as a promising solution for this disease due to their regenerative potential, which is mainly achieved through their paracrine function.
Study of mdMSCs’ Effects and Underlying Molecular Actors
- The effects of co-culturing cartilage explant with mdMSCs were studied by measuring the release of glycosaminoglycan (a compound prevalent in cartilage) and nitric oxide production.
- Amino acids in cell culture-based secreted protein analyses were conducted to identify the underlying molecular factors contributing to these effects.
- The co-culturing of muscle-derived MSCs led to a decrease in the cytokine-induced glycosaminoglycan release by cartilage explants, indicating a protective effect of mdMSCs.
Identification of Proteins and Therapeutic Implications
- Among many sequenced proteins in the co-culture conditioned medium, abundances of two proteins — decorin and matrix metalloproteinase 3 — were found to significantly change. Western blot analyses confirmed this.
- The results suggest that muscle-derived MSCs could reduce the harmful impact of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of an enzyme called matrix metalloproteinase 3 and by increasing the secretion of the protein decorin.
- These alterations could help reduce the damaging consequences of cartilage exposure to pro-inflammatory cytokines, suggesting that the use of mdMSCs could be a viable treatment for conditions like osteoarthritis.
- The beneficial effects can be explained by the bioactives secreted by mdMSCs, such as TIMP-1 and decorin, which act as an inhibitor of the harmful enzyme matrix metalloproteinase 3 and as an anti-inflammatory protein respectively.
Cite This Article
APA
Dechêne L, Colin M, Demazy C, Fransolet M, Niesten A, Arnould T, Serteyn D, Dieu M, Renard P.
(2022).
Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model.
Stem Cell Rev Rep, 19(2), 550-567.
https://doi.org/10.1007/s12015-022-10463-4 Publication
Researcher Affiliations
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium.
- Department of Clinical Sciences, Anesthesiology and Equine Surgery, Faculty of Veterinary Medicine, B41, University of Liege, Sart Tilman, 4000, Liège, Belgium.
- Department of Pharmacotherapy and Pharmaceuticals, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), 1050, Brussels, Belgium.
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium.
- Mass Spectrometry Platform (MaSUN) - Namur Research Institute for Life Sciences (Narilis), University of Namur (UNamur), 5000, Namur, Belgium.
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium.
- Mass Spectrometry Platform (MaSUN) - Namur Research Institute for Life Sciences (Narilis), University of Namur (UNamur), 5000, Namur, Belgium.
- Centre of Oxygen, Research and Development (CORD), Institute of Chemistry B6a, University of Liege (ULiège), Sart Tilman, 4000, Liège, Belgium.
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium.
- Department of Clinical Sciences, Anesthesiology and Equine Surgery, Faculty of Veterinary Medicine, B41, University of Liege, Sart Tilman, 4000, Liège, Belgium.
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium.
- Mass Spectrometry Platform (MaSUN) - Namur Research Institute for Life Sciences (Narilis), University of Namur (UNamur), 5000, Namur, Belgium.
- Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Rue de Bruxelles 61, 5000, Namur, Belgium. patsy.renard@unamur.be.
- Mass Spectrometry Platform (MaSUN) - Namur Research Institute for Life Sciences (Narilis), University of Namur (UNamur), 5000, Namur, Belgium. patsy.renard@unamur.be.
MeSH Terms
- Animals
- Cartilage / metabolism
- Chondrocytes
- Cytokines / metabolism
- Decorin / metabolism
- Decorin / pharmacology
- Glycosaminoglycans / metabolism
- Horses
- Matrix Metalloproteinase 3 / metabolism
- Matrix Metalloproteinase 3 / pharmacology
- Mesenchymal Stem Cells
- Muscles / metabolism
- Osteoarthritis / therapy
- Osteoarthritis / veterinary
Conflict of Interest Statement
DS got patent for mdMSCs (WO2015091210). DS is administrator of RevaTis company, the provider of mdMSCs. Other authors have no conflict of interest.
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Citations
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