The preventive effects of two nutraceuticals on experimentally induced acute synovitis

Abstract

SummaryBackgroundNutraceuticals are often used in the management of equine osteoarthritis, but scientific evidence of their efficacy is lacking.ObjectivesTo study the preventive effects of two new nutraceuticals after the experimental induction of synovitis in comparison with positive and negative control treatments.Study designBlinded, controlled, randomised experiment.MethodsTwenty‐four healthy Standardbred horses were randomly allocated to supplement AT (multi‐ingredient, 28 days), supplement HP (collagen hydrolysate, 60 days), meloxicam (4 days) or placebo (60 days). Synovitis was induced in the right intercarpal joint by intra‐articular injection of 0.5 ng lipopolysaccharide (LPS) of Escherichia coli while treatments were continued. Blood and synovial fluid were sampled before treatment, immediately prior to LPS injection, and at 8, 24 and 48 h post‐injection. Synovial fluid samples were analysed for total nucleated cell count (TNCC), total protein (TP) and selected biomarkers (prostaglandin E2 [PGE 2], interleukin‐6 [IL‐6], glycosaminoglycans [GAGs], type II collagen synthesis [CPII], matrix metalloproteinase [MMP]). Lameness was scored by visual examination and pressure plate analysis immediately prior to LPS injection, and at 8, 24 and 48 h post‐injection. Clinical examinations were performed before treatment, immediately prior to LPS injection, at 2, 4 and 6 h post‐injection, and then twice per day during the test period.ResultsBefore treatment and intra‐articular challenge, there were no statistically significant differences among the treatment groups for any of the parameters. After intra‐articular challenge, the placebo group showed significantly higher synovial fluid TP, TNCC and PGE 2 compared with the meloxicam group, although the model did not induce a relevant amount of lameness. Both nutraceuticals resulted in significantly lower synovial fluid TP, TNCC and PGE 2 compared with placebo. No statistical differences in IL‐6, GAGs, CPII or MMPs were observed among treatment groups. No adverse effects were observed.Main limitationsDespite evidence of synovitis, lameness was too mild to detect.ConclusionsThe preventive administration of these nutraceuticals showed anti‐inflammatory effects in this validated synovitis model. Therefore, further studies of their clinical applicability are warranted.

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy

“…PGE 2 , frequently considered a marker of inflammation, also exhibits anti-inflammatory and anabolic properties, including chondrocyte protection and activation of pro-resolving macrophages. 21,62,[102][103][104] In fact, PGE 2 generated during the early stages of inflammation upregulates the synthesis of specialized pro-resolving molecules involved in inflammation resolution and tissue repair. 21 Increasing concentrations of PGE 2 in both SF and ISF could result from the metabolism of arachidonic acid from phagocytosed dead cells, especially considering the absence of inflammatory triggers in SF.…”

“…[119][120][121][122][123] Although it is a model of acute synovitis, it does induce significant increases in synovial fluid MMP activity and markers of type II collagen and proteoglycan degradation (C2C and 3-B-3) and synthesis (CPII and CS-846) that last for at least 1 week. 103,119,124 Moreover, if sustained by weekly stimulation for up to 12 weeks, the synovitis model induces hallmark features of OA in the synovium and cartilage in addition to clinical and radiographic changes, comparable to naturally occurring OA. [125][126][127] Given the strong agreement between our in vitro model and our in vivo study treating acute synovitis with BMNC, 37 this in vitro model should be considered for future studies assessing the mechanism of articular cell biology, pathobiology, and drug testing.…”

Comparative analysis of macrophage activation in the synovium of healthy and osteoarthritic equine joints

“…Recent proteomic analysis of synovial fluid and genome-wide transcriptomic analysis of cartilage comparing samples from OA and healthy joints did not identify IL-1 or TNF-α as central targets (92,93). PGE2 has also been used as an important marker of joint inflammation (8,94,95). However, PGE2 also plays anti-inflammatory and anabolic roles such as inhibition of inflammatory cytokines and neutrophil infiltration to the site of injury, chondrocyte protection, and activation of pro-resolving macrophages (18,46,96,97).…”

Exploring relationships between body condition score, body fat, activity level and inflammatory biomarkers

“…Two of the most common and physiologically relevant biomarkers used to predict inflammation and/or OA in horses are prostaglandin E 2 (PGE 2 ) and glycosaminoglycan (GAG). PGE 2 has a central role in initiation and/or propagation of articular inflammation and is persistently over-produced in arthritis (van Loon et al, 2010;van de Water et al, 2017). Synovial fluid PGE 2 has long been recognized as having excellent predictive value for joint disease in horses (Bertone, Palmer, & Jones, 2001).…”