title: Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Comparative Orthopedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine vétérinaire, Université de Montréal, St Hyacinthe, QC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Vézina Audette
authors.forename: A
authors.initials: A
authors.lastname: Lavoie-Lamoureux
authors.forename: J-P
authors.initials: JP
authors.lastname: Lavoie
authors.forename: S
authors.initials: S
authors.lastname: Laverty
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006734:Horse Diseases / Q000378:metabolism / Q000473:pathology*; D006736:Horses; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D019899:Paracrine Communication / Q000187:drug effects* / Q000235:genetics; D013582:Synovial Fluid / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides
keywords: Cartilage; Equine; Horse; Mesenchymal stem cells; Multipotent mesenchymal stromal cells; Osteoarthritis; Paracrine communication; Reverse transcriptase polymerase chain reaction; Stem cells; Synovial fluid