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Arthritis research & therapy2009; 11(2); R35; doi: 10.1186/ar2640

Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study.

Abstract: Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation. Methods: Localized inflammation was induced in the intercarpal joint of six horses by sterile injection of 0.5 ng lipopolysaccharide, and synovial fluid was collected at post-injection hours (PIH) 0, 8, 24 and 168. Concentrations of inflammatory mediators (prostaglandin E2, substance P, and bradykinin), general matrix metalloproteinase activity and markers of collagen II turnover (CPII and C2C) as well as aggrecan turnover (CS846 and glycosaminoglycans) were measured with appropriate assays. One-way analysis of variance on repeated measures was used to analyze differences in synovial fluid marker levels over time. Results: Lipopolysaccharide-injection led to a sharp rise in prostaglandin E2 at PIH 8, while substance P, bradykinin and matrix metalloproteinase activity showed more sustained increases at PIH 8 and 24. Glycosaminoglycan release paralleled changes in the CS846 epitope, with an increase by PIH 8, a peak at PIH 24, and return to baseline by PIH 168. For type II collagen, a parallel time course between catabolic (C2C) and anabolic (CPII) markers was also observed, but the time course differed from that seen for proteoglycan markers: collagen II markers peaked later, at PIH 24, and were still elevated over baseline at PIH 168. Conclusions: A primary intra-articular inflammatory insult, characterized by local release of peptide and lipid mediators and matrix metalloproteinase activation, can alter synovial fluid levels of proteoglycan biomarkers as early as 8 hours post-induction, and can lead to sustained rises in collagen II biomarkers during at least 1 week after onset.
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Publication Date: 2009-03-09 PubMed ID: 19272138PubMed Central: PMC2688180DOI: 10.1186/ar2640Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research aimed to understand the changes that occur in joint inflammation, particularly regarding biomarkers in synovial fluid. The researchers induced inflammation in the joints of six horses and monitored the fluctuations in inflammatory mediators, enzyme activity, and cartilage biomarkers over a period of one week. They discovered that inflammation can rapidly affect synovial fluid levels of specific biomarkers and leads to sustained increases in collagen II biomarkers for at least a week after onset.

Methodology

  • The research team induced localized inflammation in the intercarpal joint of six horses by sterile injection of 0.5 ng lipopolysaccharide.
  • Synovial fluid was extracted from each horse at four different post-injection hours (PIH) – 0, 8, 24 and 168.
  • Specific inflammatory mediators in the collected synovial fluid including prostaglandin E2, substance P, and bradykinin were measured with appropriate assays.
  • Alongside, they also gauged the general matrix metalloproteinase activity (enzymes that contribute to the breakdown of matrix tissues) and markers of collagen II turnover (CPII and C2C), and aggrecan turnover (CS846 and glycosaminoglycans).
  • One-way analysis of variance on repeated measures was used to compare differences in synovial fluid marker levels over time.

Results

  • Lipopolysaccharide injection resulted in a steep surge in prostaglandin E2 at PIH 8. Substance P, bradykinin, and matrix metalloproteinase activity, however, showed sustained elevations at PIH 8 and 24.
  • Release of glycosaminoglycan mirrored changes in the CS846 epitope, with an enhancement by PIH 8, a peak at PIH 24, and an eventual return to baseline by PIH 168.
  • As for type II collagen, both catabolic (C2C) and anabolic (CPII) markers had a similar time course but differed from the time course of proteoglycan markers. Collagen II markers displayed a peak later, at PIH 24, and remained beyond the baseline at PIH 168.

Conclusions

  • The research confirmed that primary intra-articular inflammation can rapidly alter synovial fluid levels of proteoglycan biomarkers as early as 8 hours after induction.
  • It also demonstrated that inflammation can lead to sustained rises in collagen II biomarkers for at least 1 week after onset. This inflammatory insult is accompanied by the local release of peptide and lipid mediators and matrix metalloproteinase activation.

This study offers valuable insights into the dynamics of joint inflammation and its potential implications on the progression and diagnosis of joint diseases.

Cite This Article

APA
de Grauw JC, van de Lest CH, van Weeren PR. (2009). Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther, 11(2), R35. https://doi.org/10.1186/ar2640

Publication

Arthritis research & therapy
ISSN: 1478-6362
NlmUniqueID: 101154438
Country: England
Language: English
Volume: 11
Issue: 2
Pages: R35

Researcher Affiliations

de Grauw, Janny C
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. j.c.degrauw@uu.nl
van de Lest, Chris H A
    van Weeren, Paul René

      MeSH Terms

      • Animals
      • Arthritis, Experimental / metabolism
      • Biomarkers / analysis
      • Cartilage, Articular / chemistry
      • Cartilage, Articular / metabolism
      • Enzyme-Linked Immunosorbent Assay
      • Female
      • Horses
      • Inflammation Mediators / analysis
      • Inflammation Mediators / metabolism
      • Synovial Fluid / chemistry
      • Synovial Fluid / metabolism

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