Nutritional targeting of inflammatory pathways and catabolic mediators involved in equine osteoarthritis

Clutterbuck, A.

Nutritional targeting of inflammatory pathways and catabolic mediators involved in equine osteoarthritis

Publication Date

July 22, 2011

Creator

Clutterbuck, A.

Abstract

Osteoarthritis (OA) is a degenerative disease of synovial joints with an inflammatory component, which affects humans and companion animals, including horses. Current pharmacotherapy for OA is associated with deleterious side effects. Therefore, plant-derived products with anti-inflammatory properties may provide safer natural alternatives. The project aimed to use in vitro models of equine cartilage to test the hypothesis that plant-derived extracts would reduce inflammation and degradation in an explant model of early OA. The anti-inflammatory polyphenol, curcumin, significantly reduced interleukin-1 beta (lL-1β)-stimulated glycosaminoglycan, matrix metalloproteinase-3 and prostaglandin E[subscript]2 release in the explant model. Using a cocktail of plant extracts illustrated how different effects were observed depending on the solvent used to dissolve the raw material. Chondrocyte monolayers were used to determine that counteraction of IL-1β- stimulated effects in the explant model occurred at non-cytotoxic concentrations. The explant model was adapted for proteomic studies of the cartilage secretome. Several proteins involved in matrix function and degradation were identified. This adaptation may further our understanding of the processes in the early OA explant model and may facilitate studying the effects of anti-inflammatory compounds on the secretome. A concurrent field trial showed that the plant extract cocktail did not significantly improve mobility in horses with chronic hindlimb stiffness. However, it illustrated the need for practical, more objective markers to help select animals of similar disease status and determine effects in the joints. Therefore, the proteomic study highlighted the potential for in vitro models to support field trials by identifying in vivo biomarkers for diagnosing early OA and assessing therapeutic responses. In conclusion, in vitro models of equine cartilage have considerable potential for assessing the ability of plant extracts to target inflammatory pathways and catabolic mediators in OA. The data presented suggests that nutritional intervention using plant-derived extracts with putative anti-inflammatory properties may support equine joint health.

Item Type

ethesis

Thesis Type

PhD

Supervisors

Bowen, M.

Freeman, S.L.

Mobasheri, A.