Osteoarthritis and cartilage2013; 21(8); 1116-1124; doi: 10.1016/j.joca.2013.05.004

Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells.

Abstract: Osteoarthritis (OA) is a degenerative disease of joint tissues that causes articular cartilage erosion, osteophytosis and loss of function due to pain. Inflammation and inflammatory cytokines in synovial fluid (SF) contribute to OA progression. Intra-articular (IA) injections of multipotent mesenchymal stromal cells (MSCs) are employed to treat OA in both humans and animals. MSCs secrete paracrine pro-inflammatory and anabolic signaling molecules that promote tissue repair. The objective of this study was to investigate the effects of OASF on the gene expression of paracrine signaling molecules by MSCs. Methods: The effects of Lipopolysaccharide (LPS) and interleukin (IL)-1β as well as both normal (N) and osteoarthritis (OA) SF stimulations on the expression of paracrine pro-inflammatory (tumor necrosis factor (TNF)-α, IL-1β, IL-8), modulatory (IL-6) and anabolic (vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and insulin-like growth factor (IGF)-1) signaling molecules by equine bone marrow multipotent mesenchymal stromal cells (eBM-MSCs) was investigated employing reverse transcriptase-polymerase chain reaction (RT-PCR). Results: In contrast with NSF, OASF significantly up-regulated the expression of VEGF in eBM-MSCs. Both NSF and OASF significantly down-regulated the expression of IL-1β. LPS and IL-1β significantly increased the expression of pro-inflammatory cytokines (TNF-α, IL-8 and IL-6; and IL-1β and IL-8 respectively). Conclusions: We conclude that the transcription of paracrine signaling molecules in eBM-MSCs is modulated by SF. Furthermore, OA alters the properties of SF and the response of eBM-MSCs. Finally, the effects of LPS or IL-1β stimulation are distinct to that observed following stimulations with OASF.
Publication Date: 2013-05-14 PubMed ID: 23685224DOI: 10.1016/j.joca.2013.05.004Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates how inflammatory stimuli affect the gene expression of signaling molecules in bone marrow multipotent mesenchymal stromal cells. Key findings reveal significant up-regulation of certain molecules due to synovial fluid from osteoarthritis patients, highlighting the role of this fluid in disease progression and potential approaches to treatment.

Objectives and Methods

  • The study aimed to explore the impact of the osteoarthritis synovial fluid (OASF) on the gene expression of paracrine signaling molecules produced by multipotent mesenchymal stromal cells (MSCs)
  • The researchers used Lipopolysaccharide (LPS) and Interleukin-1β, along with both normal (N) and osteoarthritis (OA) synovial fluids to stimulate the MSCs
  • The expression of pro-inflammatory, modulatory, and anabolic signaling molecules was then investigated using reverse transcriptase-polymerase chain reaction (RT-PCR)

Key Findings

  • OASF significantly increased the expression of vascular endothelial growth factor (VEGF) in equine bone marrow multipotent mesenchymal stromal cells (eBM-MSCs)
  • Both N and OASF synovial fluids led to a significant decrease in the expression of interleukin-1β, a pro-inflammatory cytokine
  • LPS and interleukin-1β notably raised the production of pro-inflammatory cytokines, namely tumor necrosis factor-α, interleukin-8, and interleukin-6

Conclusions

  • The study concludes that synovial fluid can alter the transcription of paracrine signaling molecules in eBM-MSCs, pointing out different responses to OASF compared to other inflammatory stimuli
  • The findings suggest that osteoarthritis changes the properties of the synovial fluid, which further impacts the response of eBM-MSCs
  • The effects following inflammatory stimuli using LPS or interleukin-1β are distinct from those observed when using OASF
  • These findings have potential implications for the development of therapeutic approaches to OA, by manipulating the paracrine signaling molecules of MSCs

Cite This Article

APA
Vézina Audette R, Lavoie-Lamoureux A, Lavoie JP, Laverty S. (2013). Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells. Osteoarthritis Cartilage, 21(8), 1116-1124. https://doi.org/10.1016/j.joca.2013.05.004

Publication

ISSN: 1522-9653
NlmUniqueID: 9305697
Country: England
Language: English
Volume: 21
Issue: 8
Pages: 1116-1124

Researcher Affiliations

Vézina Audette, R
  • Comparative Orthopedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine vétérinaire, Université de Montréal, St Hyacinthe, QC, Canada.
Lavoie-Lamoureux, A
    Lavoie, J-P
      Laverty, S

        MeSH Terms

        • Animals
        • Cells, Cultured
        • Gene Expression Regulation / drug effects
        • Horse Diseases / metabolism
        • Horse Diseases / pathology
        • Horses
        • Inflammation Mediators / metabolism
        • Inflammation Mediators / pharmacology
        • Intercellular Signaling Peptides and Proteins / biosynthesis
        • Intercellular Signaling Peptides and Proteins / genetics
        • Interleukin-1beta / pharmacology
        • Lipopolysaccharides / pharmacology
        • Mesenchymal Stem Cells / drug effects
        • Mesenchymal Stem Cells / metabolism
        • Mesenchymal Stem Cells / physiology
        • Osteoarthritis / metabolism
        • Osteoarthritis / pathology
        • Osteoarthritis / veterinary
        • Paracrine Communication / drug effects
        • Paracrine Communication / genetics
        • Synovial Fluid / chemistry
        • Transcription, Genetic / drug effects

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