Characteristic Inflammatory Biomarkers in an Equine Model of Persistent Synovitis Induced By the Intra-Articular Administration of Monoiodoacetic Acid

J Equine Vet Sci. 2023 Aug:127:104564. doi: 10.1016/j.jevs.2023.104564. Epub 2023 May 18.

Abstract

Persistent synovitis damages the articular cartilage in horses. To evaluate the effectiveness of treatment for synovitis using a model induced by intra-articular administration of monoiodoacetic acid (MIA), it is necessary to identify inflammatory biomarkers characteristic of the MIA model. Synovitis was induced by administering MIA into the unilateral antebrachiocarpal joints of five horses, and saline was injected into the contralateral joints as a control on day 0. Clinical and ultrasonographic examinations and synovial fluid collection were performed on days 0, 1, 2, 7, 14, 21, 28, and 35. Leukocyte, lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and transforming growth factor-β1 (TGF-β1) concentrations in the synovial fluid were measured. Synovium was obtained after euthanasia on day 42 and histologically examined before quantification of the gene expression of inflammatory biomarkers by real-time PCR. Acute inflammatory symptoms persisted for approximately 2 weeks before returning to control levels. However, some indicators of chronic inflammation remained elevated until day 35. On day 42, synovitis continued histologically, with osteoclasts. The expressions of matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), receptor activator of nuclear factor kappa-Β ligand (RANKL), and collagen type I α2 chain (Col1a2) were significantly higher in the MIA model than in the control. In the MIA model, representative inflammatory biomarkers in the chronic inflammatory stage were persistently expressed in both synovial fluid and tissue, suggesting that they may be useful for the assessment of the anti-inflammatory effect of drugs.

Keywords: Inflammatory biomarker; Monoiodoacetic acid; Osteoarthritis; Persistent synovitis; Synovium.

MeSH terms

  • Animals
  • Biomarkers
  • Collagen Type I / adverse effects
  • Horse Diseases* / chemically induced
  • Horse Diseases* / drug therapy
  • Horse Diseases* / metabolism
  • Horses
  • Iodoacetic Acid / adverse effects
  • Synovitis* / chemically induced
  • Synovitis* / drug therapy
  • Synovitis* / metabolism
  • Synovitis* / veterinary

Substances

  • Collagen Type I, alpha2 Subunit
  • Iodoacetic Acid
  • Collagen Type I
  • Biomarkers