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PloS one2012; 7(11); e48978; doi: 10.1371/journal.pone.0048978

Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.

Abstract: The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2) (PGE(2)), F(2α) (PGF(2α)), lipoxin A(4) (LXA(4)) and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2) metabolism, microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and EP(4) receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants.Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2) and elevated LXA(4) levels compared to normal and chronic injuries. In contrast, PGF(2α) levels remained unchanged and were three-fold lower than PGE(2). The synthetic capacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4) receptor were unchanged. Paradoxically low tendon PGE(2) levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2) is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4) levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2) levels in injury. Furthermore, uninjured tendon explants from younger (<10 years) but not older horses (≥10 years) treated with IL-1β responded by increasing FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve inflammation via FPR2/ALX, which may present a potential mechanism for development of chronic tendinopathy and re-injury.
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Publication Date: 2012-11-14 PubMed ID: 23155437PubMed Central: PMC3498370DOI: 10.1371/journal.pone.0048978Google Scholar: Lookup
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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 study investigates the role of inflammation and specific chemicals, known as arachidonic acid metabolites, in the development and progression of tendon disease. The study focuses on horses, but the findings may also apply to other species.

Study Methods and Material

  • The study analyzed the levels of four specific chemicals (prostaglandins E(2) and F(2α), lipoxin A(4) and its receptor FPR2/ALX) in extracts of healthy and diseased tendons in horses that had naturally occurring tendon injury.
  • They assessed both early stage, or sub-acute, and chronic forms of tendon injury.
  • They also investigated the expression of additional compounds related to inflammation and tendon metabolism, including microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and the EP(4) receptor.
  • They used tendon explants, or tissue extracted from the horses, to evaluate how tendons respond to an inflammation stimulus.

Key Findings

  • The study found varied levels of the studied chemicals between healthy and injured tendons, and depending on the stage of injury.
  • Injured tendons in the sub-acute stage had low levels of PGE(2) and elevated levels of LXA(4), unlike healthy and chronically injured tendons.
  • The study suggests that an imbalance in the synthesis and clearance of PGE(2) could contribute to tendon inflammation and its resolution.
  • Interestingly, age played a role in the levels of another chemical, FPR2/ALX. Uninjured tendons from younger horses (less than 10 years old) increased their expression of this receptor in response to an inflammatory stimulus, unlike tendons from older horses. This suggests that older individuals may have a reduced capacity to resolve inflammation via FPR2/ALX, which could contribute to the development of chronic tendon disease and reinjury.

Implications for Veterinary Medicine

  • These findings contribute to a better understanding of the biological processes involved in tendon disease and could help veterinarians develop better treatment approaches.
  • By uncovering the role of inflammation and specific chemicals in tendon disease, the study may pave the way for the development of targeted therapies.
  • Given the involvement of age in disease progression, the research could also lead to specialized treatment plans for horses of different ages.

Cite This Article

APA
Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK. (2012). Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease. PLoS One, 7(11), e48978. https://doi.org/10.1371/journal.pone.0048978

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 7
Issue: 11
Pages: e48978
PII: e48978

Researcher Affiliations

Dakin, Stephanie Georgina
  • Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hatfield, United Kingdom. sdakin@rvc.ac.uk
Dudhia, Jayesh
    Werling, Natalie Jayne
      Werling, Dirk
        Abayasekara, Dilkush Robert Ephrem
          Smith, Roger Kenneth Whealands

            MeSH Terms

            • Aging / metabolism
            • Animals
            • Dinoprost / metabolism
            • Dinoprostone / metabolism
            • Horses
            • Inflammation / metabolism
            • Lipoxins / metabolism
            • Receptors, Formyl Peptide / metabolism
            • Receptors, Lipoxin / metabolism
            • Tendinopathy / metabolism
            • Tendon Injuries / metabolism
            • Tendons / metabolism

            Grant Funding

            • BB/F018258/1 / Biotechnology and Biological Sciences Research Council

            Conflict of Interest Statement

            The authors declare the study was in part funded by Ceva (France). There are no other relevant declarations relating to employment, consultancy, patents, products in development or marketed products. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

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