Abstract

BackgroundInflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL).ResultsOperation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations but compared with baseline, synovial fluid IL-1ra and TNF-α concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen.ConclusionsCreation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-α concentrations but changes in concentrations of anabolic growth factors TGF-β1 and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.

Highlights

  • Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers

  • Statistical methods interleukin-1 receptor antagonist (IL-1ra), plateletderived growth factor BB (PDGF-BB), transforming growth factor beta 1 (TGF-β1), tumour necrosis factor alpha (TNF-α), White blood cell (WBC) count and total protein (TP) concentration were analysed with analysis of covariance models (ANCOVA)

  • The change in biomarker and TP concentrations and WBC count from pre-operation to pre-treatment was examined in one analysis and the change from pretreatment to end of follow-up in another analysis

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Summary

Introduction

Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injec‐ tion, alone or in combination with other substances, has been examined only in a few equine studies. Inflammatory and degenerative activity in the joint can be studied in vivo by analysis of synovial fluid (SF) biomarkers, such as pro-inflammatory cytokines in experimental setting [1,2,3,4,5], or in naturally occurring joint disease [6,7,8]. In animal models HA has been demonstrated to reduce pain via protecting nociceptive nerve endings [16] and by blocking pain receptor channels [17]

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