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...
Main Authors: | , , , |
---|---|
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 |
_version_ | 1797856253708337152 |
---|---|
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. |
first_indexed | 2024-04-09T20:37:23Z |
format | Article |
id | doaj.art-ff0bc127129d4eefb376fa65e6cf0779 |
institution | Directory Open Access Journal |
issn | 0891-6640 1939-1676 |
language | English |
last_indexed | 2024-04-09T20:37:23Z |
publishDate | 2023-03-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Veterinary Internal Medicine |
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 |
work_keys_str_mv | AT teresaaburns digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing AT mauriarwatts digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing AT jameskbelknap digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing AT andrewwvaneps digitallamellarinflammatorysignalinginanexperimentalmodelofequinepreferentialweightbearing |