Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing

Abstract Background Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life‐limiting, yet the pathophysiology remains obscure. Hypothesis/Objectives To investigate the role of digital lamellar inflammatory signaling in the pathophysiology of SLL usi...

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Main Authors: Teresa A. Burns, Mauria R. Watts, James K. Belknap, Andrew W. vanEps
Format: Article
Language:English
Published: Wiley 2023-03-01
Series:Journal of Veterinary Internal Medicine
Subjects:
Online Access:https://doi.org/10.1111/jvim.16662
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author Teresa A. Burns
Mauria R. Watts
James K. Belknap
Andrew W. vanEps
author_facet Teresa A. Burns
Mauria R. Watts
James K. Belknap
Andrew W. vanEps
author_sort Teresa A. Burns
collection DOAJ
description Abstract Background Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life‐limiting, yet the pathophysiology remains obscure. Hypothesis/Objectives To investigate the role of digital lamellar inflammatory signaling in the pathophysiology of SLL using a model of unilateral weight bearing, hypothesizing that there would be evidence of lamellar inflammation in limbs subjected to the model. Animals Thirteen healthy adult Standardbred horses were used for this study (11 geldings, 2 mares; mean age 6.5 ± 2.5 years; mean body weight 458.3 ± 32.8 kg). Methods Randomized controlled experimental study. A steel shoe with a custom insert was applied to a randomly selected front foot of 7 horses; 6 horses were unshod and served as controls. After 92 hours, all horses were humanely euthanized, and digital lamellar samples were collected. Lamellar protein and mRNA were isolated and used to perform western blot and PCR. Results Lamellar concentrations of IL‐6 mRNA were higher in SL tissue than IL HIND tissue (median [25%‐75%] normalized copy number 191 [111‐3060] and 48 [25‐74], respectively; P=.003), and lamellar concentrations of COX‐2 mRNA were higher in SL tissue than CON tissue (normalized copy number 400 [168‐634] and 125 [74‐178], respectively; P=.007). Lamellar concentrations of IL‐1B, IL‐10, and COX‐1 mRNA were not significantly different between groups. The concentrations of phosphorylated (activated) STAT1 and STAT3 proteins were higher in SL (0.5 [0.35‐0.87] and 1.35 [1.1‐1.7], respectively) compared to CON (0.24 [0.09‐0.37] and 0.31 [0.16‐037]) and UL HIND (0.27 [0.19‐0.37] and 0.38 [0.24‐0.5]); P=0.01 and P<0.001. Conclusions and Clinical Importance Lamellar inflammatory signaling was higher in tissue from horses subjected to prolonged unilateral weight‐bearing, suggesting that these pathways could be relevant to the pathophysiology of SLL.
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spelling doaj.art-ff0bc127129d4eefb376fa65e6cf07792023-03-30T07:47:06ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762023-03-0137268168810.1111/jvim.16662Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearingTeresa A. Burns0Mauria R. Watts1James K. Belknap2Andrew W. vanEps3The Ohio State University College of Veterinary Medicine Columbus Ohio USAThe Ohio State University College of Veterinary Medicine Columbus Ohio USAThe Ohio State University College of Veterinary Medicine Columbus Ohio USASchool of Veterinary Science University of Queensland Gatton Queensland AustraliaAbstract Background Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life‐limiting, yet the pathophysiology remains obscure. Hypothesis/Objectives To investigate the role of digital lamellar inflammatory signaling in the pathophysiology of SLL using a model of unilateral weight bearing, hypothesizing that there would be evidence of lamellar inflammation in limbs subjected to the model. Animals Thirteen healthy adult Standardbred horses were used for this study (11 geldings, 2 mares; mean age 6.5 ± 2.5 years; mean body weight 458.3 ± 32.8 kg). Methods Randomized controlled experimental study. A steel shoe with a custom insert was applied to a randomly selected front foot of 7 horses; 6 horses were unshod and served as controls. After 92 hours, all horses were humanely euthanized, and digital lamellar samples were collected. Lamellar protein and mRNA were isolated and used to perform western blot and PCR. Results Lamellar concentrations of IL‐6 mRNA were higher in SL tissue than IL HIND tissue (median [25%‐75%] normalized copy number 191 [111‐3060] and 48 [25‐74], respectively; P=.003), and lamellar concentrations of COX‐2 mRNA were higher in SL tissue than CON tissue (normalized copy number 400 [168‐634] and 125 [74‐178], respectively; P=.007). Lamellar concentrations of IL‐1B, IL‐10, and COX‐1 mRNA were not significantly different between groups. The concentrations of phosphorylated (activated) STAT1 and STAT3 proteins were higher in SL (0.5 [0.35‐0.87] and 1.35 [1.1‐1.7], respectively) compared to CON (0.24 [0.09‐0.37] and 0.31 [0.16‐037]) and UL HIND (0.27 [0.19‐0.37] and 0.38 [0.24‐0.5]); P=0.01 and P<0.001. Conclusions and Clinical Importance Lamellar inflammatory signaling was higher in tissue from horses subjected to prolonged unilateral weight‐bearing, suggesting that these pathways could be relevant to the pathophysiology of SLL.https://doi.org/10.1111/jvim.16662cytokinesinflammationischemiaJAK/STATstretch
spellingShingle Teresa A. Burns
Mauria R. Watts
James K. Belknap
Andrew W. vanEps
Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
Journal of Veterinary Internal Medicine
cytokines
inflammation
ischemia
JAK/STAT
stretch
title Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
title_full Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
title_fullStr Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
title_full_unstemmed Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
title_short Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
title_sort digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
topic cytokines
inflammation
ischemia
JAK/STAT
stretch
url https://doi.org/10.1111/jvim.16662
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AT jameskbelknap digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing
AT andrewwvaneps digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing