Effects of pro-inflammatory cytokines on chondrogenesis of equine mesenchymal stromal cells derived from bone marrow or synovial fluid.
Abstract: Mesenchymal stromal cells (MSCs) have the capacity to differentiate into cells of mesenchymal lineage, such as chondrocytes, and have potential for use in regeneration of equine articular cartilage. MSCs instilled intra-articularly would be exposed to the inflamed environment associated with equine osteoarthritis (OA), which may compromise their function and ability to heal a cartilaginous defect. The aim of this study was to assess the ability of equine adult MSCs to differentiate into chondrocytes when stimulated with pro-inflammatory cytokines. MSCs derived from equine bone marrow (BM) and from synovial fluid (SF) were cultured in chondrogenic induction medium containing transforming growth factor (TGF)-β1. BM-derived MSCs (BMMSCs) and SF-derived MSCs (SFMSCs) were stimulated with 100 ng/mL interferon (IFN)-γ and 10 ng/mL tumor necrosis factor (TNF)-α. Chondrogenic differentiation was measured quantitatively with the glycosaminoglycan (GAG) assay and qualitatively by immunofluorescence (IF) for SOX-9, TGF-β1, aggrecan and collagen II. The viability of equine MSCs was maintained in the presence of IFN-γ and TNF-α, but production of GAGs from both types of MSCs was decreased in stimulated medium. Exposure of BMMSCs to pro-inflammatory cytokines reduced the levels of SOX-9, TGF-β1, aggrecan and collagen II, whereas exposure of SFMSCs to these cytokines reduced the levels of aggrecan only. These data suggest that pro-inflammatory cytokines do not affect proliferation of MSCs, but could inhibit chondrogenesis of MSCs.
Published by Elsevier Ltd.
Publication Date: 2016-05-31 PubMed ID: 27810206DOI: 10.1016/j.tvjl.2016.05.014Google Scholar: Lookup
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- Journal Article
Summary
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This research explores the impact of pro-inflammatory cytokines on the ability of specific horse stem cells to develop into chondrocytes. The findings show that these cytokines do not affect stem cell proliferation, but could limit their development into chondrocytes.
Objective of the Study
- The study aims to evaluate how pro-inflammatory cytokines affect the chondrogenesis (the process of cartilage formation) of mesenchymal stromal cells (MSCs) derived from horse bone marrow and synovial fluid. This has significance given the potential of MSCs to be used in repairing cartilage defects, particularly in the context of osteoarthritis, which is common in equines.
Methodology
- MSCs acquired from equine bone marrow and synovial fluid were cultured in a growth medium with transforming growth factor (TGF)-β1, a protein that stimulates cell growth and differentiation.
- Both types of MSCs (from bone marrow, BMMSCs, and from synovial fluid, SFMSCs) were exposed to interferon (IFN)-γ and tumor necrosis factor (TNF)-α, both of which are pro-inflammatory cytokines, substances secreted by certain cells of the immune system that have an effect on other cells.
- The researchers then measured chondrogenic differentiation quantitively using the glycosaminoglycan (GAG) assay and qualitatively through immunofluorescence for SOX-9, TGF-β1, aggrecan and collagen II, markers indicative of the chondrogenesis process.
Findings
- The study found that the viability of MSCs remained intact despite the presence of IFN-γ and TNF-α, indicating that these pro-inflammatory cytokines do not hinder cell proliferation.
- However, the production of GAGs, compounds that form part of the ground substance of cartilage, decreased for both types of MSCs in the cytokine-treated medium, signifying a potential hindrance to chondrogenesis.
- BMMSCs exposed to these cytokines also showed reduced levels of SOX-9, TGF-β1, aggrecan and collagen II, indicating a negative impact on chondrocyte differentiation. Meanwhile, SFMSCs showed only reduced levels of aggrecan when exposed to the cytokines.
In conclusion, the study suggests that while pro-inflammatory cytokines do not appear to affect the proliferation of MSCs, they could potentially negatively influence their ability to differentiate into chondrocytes. This is a significant finding for the potential use of MSCs in regenerative therapies for osteoarthritis.
Cite This Article
APA
Zayed MN, Schumacher J, Misk N, Dhar MS.
(2016).
Effects of pro-inflammatory cytokines on chondrogenesis of equine mesenchymal stromal cells derived from bone marrow or synovial fluid.
Vet J, 217, 26-32.
https://doi.org/10.1016/j.tvjl.2016.05.014 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive c247, Knoxville, TN 37996, USA; Department of Animal Surgery, College of Veterinary Medicine, South Valley University, Qena 83523, Egypt.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive c247, Knoxville, TN 37996, USA.
- Department of Animal Surgery, College of Veterinary Medicine, Assuit University, Assuit 71526, Egypt.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive c247, Knoxville, TN 37996, USA. Electronic address: mdhar@utk.edu.
MeSH Terms
- Animals
- Bone Marrow / physiology
- Cell Differentiation
- Chondrocytes / physiology
- Chondrogenesis
- Cytokines / metabolism
- Horses / physiology
- Mesenchymal Stem Cells / cytology
- Synovial Fluid / physiology
Citations
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