Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.
Authors: Dakin Stephanie Georgina, Dudhia Jayesh, Werling Natalie Jayne, Werling Dirk, Abayasekara Dilkush Robert Ephrem, Smith Roger Kenneth Whealands
Journal: PloS one
Summary
# Inflamm-aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease Equine tendon injuries frequently recur, yet the inflammatory mechanisms underpinning this chronicity remain poorly understood; this investigation examined how prostaglandins and inflammation-resolving mediators change across injury stages and with advancing age. Researchers analysed levels of key lipid mediators—prostaglandin E₂ (PGE₂), prostaglandin F₂α (PGF₂α), and lipoxin A₄ (LXA₄)—alongside their associated receptors and synthetic enzymes in normal, sub-acute and chronic equine tendons, including stimulated tendon tissue samples to assess inflammatory response capacity. Sub-acute injuries exhibited a distinctive lipid mediator profile characterised by paradoxically low PGE₂ alongside elevated LXA₄ compared to both normal and chronic tendon, with altered expression ratios of prostaglandin-synthesising and degrading enzymes suggesting aberrant PGE₂ metabolism during early injury. Most significantly, tendons from horses aged 10 years and older demonstrated markedly reduced capacity to upregulate the inflammation-resolving receptor FPR2/ALX in response to inflammatory challenge, contrasting sharply with the robust response mounted by younger horses and correlating with elevated baseline PGE₂ levels. These findings suggest that age-related decline in resolution mechanisms may underlie the elevated re-injury risk and chronic tendinopathy observed in older horses, highlighting potential therapeutic targets for enhancing the natural inflammatory resolution pathway in at-risk populations.
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Practical Takeaways
- •Age significantly impacts tendon healing capacity—horses 10 years and older show reduced ability to resolve inflammation naturally, which may inform prognosis and treatment intensity decisions for tendon injuries in older horses.
- •Early intervention during the sub-acute phase may be critical, as this is when lipid mediator profiles are most dysregulated and inflammation-resolving mechanisms are most compromised.
- •Therapies targeting inflammation resolution (rather than just suppression) or supporting FPR2/ALX signaling may be particularly beneficial for older horses with tendon injuries to overcome age-related deficits in healing.
Key Findings
- •Sub-acute tendon injuries show low PGE2 and elevated LXA4 levels compared to normal and chronic injuries, suggesting altered lipid mediator profiles during early injury stages.
- •mPGES-1:PGDH ratio is elevated in sub-acute injury indicating aberrant prostaglandin E2 metabolism in early tendon disease.
- •Age-associated decline in FPR2/ALX receptor expression occurs with concurrent increased PGE2 levels in injured tendons, with horses ≥10 years showing reduced capacity to upregulate FPR2/ALX in response to IL-1β stimulation.
- •Older horses (≥10 years) exhibit impaired inflammation-resolving capacity via the FPR2/ALX pathway compared to younger horses (<10 years), potentially explaining increased chronic tendinopathy and re-injury risk with age.