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Research article - Peer-reviewed, 2021

Dynamics of local gene regulations in synovial fluid leukocytes from horses with lipopolysaccharide-induced arthritis

Walters, Marie; Skovgaard, Kerstin; Andersen, Pia Haubro; Heegaard, Peter M. H.; Jacobsen, Stine


The role of resident cells such a synoviocytes and chondrocytes in intra-articular inflammation is wellcharacterized, however the in vivo gene expression patterns of cells (predominantly leukocytes) in the synovial fluid (SF) of an inflamed joint have never previously been investigated. The aim of this study was to investigate gene expression in SF leukocytes from the inflamed joint cavity after intra-articular lipopolysaccharide (LPS) injection in horses to improve our understanding of the temporal regulation of the intra-articular inflammatory response. Gene expression was investigated in SF samples available from six horses 2, 4, 8 16 and 24 h after experimental induction of inflammation in the radiocarpal joint by lipopolysaccharide (LPS) injection. Leukocytic expression of 43 inflammation-related genes was studied using microfluidic high throughput qPCR (Fluidigm (R)). Expression of 26 genes changed significantly over the 24 h study period, including pro- and antiinflammatory genes such as interleukin (IL)1, IL6, tumor necrosis factor (TNF), cyclooxygenase 2 (COX2), IL1 receptor antagonist (IL1RN), IL10, and superoxide dismutase 2 (SOD2), chemokine genes, apoptosis-related genes, and genes related to cartilage turnover (matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1). The inflammatory responses appeared to be regulated, as an early increase (at 2 h) in expression of the pro-inflammatory genes IL1, IL6, TNF and COX2 was rapidly followed by increased expression (at 4 h) of several anti-inflammatory genes (IL10, IL1RN and SOD2). Similarly, both pro- and anti-apoptotic gene expression as well as expression of chondrodegenerative and chondroprotective genes were activated in SF leukocytes. Thus, the inflammatory response in leukocytes infiltrating the joint in the acute stage of arthritis was well orchestrated in this single-hit LPS-induced arthritis model. This study is the first to describe gene expression patterns in SFderived leukocytes in vivo during severe joint inflammation, and the results thus expand our knowledge of basic inflammatory mechanisms in the early local response in an inflamed joint.


Leukocytes; Gene expression; Joint; Inflammation; Arthritis; Horses

Published in

Veterinary Immunology and Immunopathology
2021, volume: 241, article number: 110325
Publisher: ELSEVIER

Authors' information

Walters, Marie
University of Copenhagen
Skovgaard, Kerstin
Technical University of Denmark
Andersen, Pia Haubro (Haubro Andersen, Pia)
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Heegaard, Peter M. H.
Technical University of Denmark
Jacobsen, Stine
University of Copenhagen

UKÄ Subject classification

Clinical Science

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