FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Digital lamellar inflammatory signaling in an experimental m...
Journal of veterinary internal medicine2023; 37(2); 681-688; doi: 10.1111/jvim.16662

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

Abstract: Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life-limiting, yet the pathophysiology remains obscure. Objective: 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. Methods: 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: 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.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2023-02-24 PubMed ID: 36840365PubMed Central: PMC10061185DOI: 10.1111/jvim.16662Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores how the inflammatory signaling in a horse’s hoof lamellar tissue is affected by the model of preferential weight-bearing, which could be a potential cause of the equine condition called Supporting Limb Laminitis.

Study Design

  • The study was conducted on thirteen healthy adult Standardbred horses, consisting of eleven geldings and two mares. A randomly selected front foot of seven of these horses was fitted with a custom steel shoe, while six horses remained unshod and served as controls.
  • The model of unilateral weight bearing was applied for a period of 92 hours, following which all the horses were humanely euthanized and digital lamellar samples from each of them were collected for analysis.

Methodology

  • The lamellar protein and mRNA were isolated from the collected samples and used to conduct western blot and polymerase chain reaction (PCR) experiments.
  • The analysis involved conducting comparative studies of lamellar concentrations of various molecules, including Interleukin-6 (IL-6) mRNA, Cyclooxygenase-2 (COX-2) mRNA, Interleukin-1B (IL-1B), Interleukin-10 (IL-10), Cyclooxygenase-1 (COX-1) mRNA, and phosphorylated STAT-1 and STAT-3 proteins, across different tissue types: Supporting limb lamellar tissue (SL), Hindlimb lamellar tissue (IL HIND), and control group lamellar tissue (CON).

Results

  • The study found that lamellar concentrations of IL-6 mRNA and COX-2 mRNA were higher in the supporting limb lamellar tissue compared to their respective concentrations in the hindlimb and control group tissue.
  • However, the lamellar concentrations of IL-1B, IL-10, and COX-1 mRNA did not show any significant variations between these groups.
  • On the other hand, the concentrations of phosphorylated (or activated) STAT-1 and STAT-3 proteins resulted in higher values in the supporting limb tissue in comparison to the other two groups.

Conclusions

  • The study concluded that the lamellar inflammatory signaling was higher in the tissue collected from horses subjected to prolonged unilateral weight-bearing. This result suggests that such pathways of inflammatory signaling could be crucial in understanding the underlying pathophysiology of Supporting Limb Laminitis.

Cite This Article

APA
Burns TA, Watts MR, Belknap JK, van Eps AW. (2023). Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing. J Vet Intern Med, 37(2), 681-688. https://doi.org/10.1111/jvim.16662

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 37
Issue: 2
Pages: 681-688

Researcher Affiliations

Burns, Teresa A
  • The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
Watts, Mauria R
  • The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
Belknap, James K
  • The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
van Eps, Andrew W
  • School of Veterinary Science, University of Queensland, Gatton, Queensland, Australia.
  • School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.

MeSH Terms

  • Animals
  • Female
  • Male
  • Foot Diseases / physiopathology
  • Foot Diseases / veterinary
  • Hoof and Claw
  • Horse Diseases / physiopathology
  • Horses
  • Inflammation / physiopathology
  • Inflammation / veterinary
  • RNA, Messenger / isolation & purification
  • Weight-Bearing / physiology
  • Models, Biological
  • Signal Transduction / physiology

Grant Funding

  • Grayson-Jockey Club Research Foundation

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 40 references
  1. Baxter GM, Morrison S. Complications of unilateral weight bearing.. Vet Clin North Am Equine Pract 2008;24(3):621‐642. ix.
    pubmed: 19203705
  2. Virgin JE, Goodrich LR, Baxter GM. Incidence of support limb laminitis in horses treated with half limb, full limb or transfixation pin casts: a retrospective study of 113 horses (2000‐2009).. Equine Vet J Suppl 2011;40:7‐11.
    pubmed: 22082439
  3. van Eps A, Collins SN, Pollitt CC. Supporting limb laminitis.. Vet Clin North Am Equine Pract 2010;26(2):287‐302.
    pubmed: 20699176
  4. Medina‐Torres CE, Underwood C, Pollitt CC. The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis.. Equine Vet J 2016;48(1):114‐119.
    pubmed: 25303010
  5. Medina‐Torres CE, Pollitt CC, Underwood C. Equine lamellar energy metabolism studied using tissue microdialysis.. Vet J 2014;201(3):275‐282.
    pubmed: 24947715
  6. van Eps AW, Belknap JK, Schneider X. Lamellar perfusion and energy metabolism in a preferential weight bearing model.. Equine Vet J 2021;53(4):834‐844.
    pubmed: 32986263
  7. Cao W, Zhang D, Li Q. Biomechanical stretch induces inflammation, proliferation, and migration by activating NFAT5 in arterial smooth muscle cells.. Inflammation 2017;40(6):2129‐2136.
    pubmed: 28840417
  8. Leise BS, Faleiros RR, Watts M. Hindlimb laminar inflammatory response is similar to that present in forelimbs after carbohydrate overload in horses.. Equine Vet J 2012;44:633‐639.
    pubmed: 22212091
  9. Faleiros RR, Leise BB, Westerman T, Yin C, Nuovo GJ, Belknap JK. In vivo and in vitro evidence of the involvement of CXCL1, a keratinocyte‐derived chemokine, in equine laminitis.. J Vet Intern Med 2009;23(5):1086‐1096.
    pubmed: 19572911
  10. Leise BS, Yin C, Pettigrew A. Proinflammatory cytokine responses of cultured equine keratinocytes to bacterial pathogen‐associated molecular pattern motifs.. Equine Vet J 2010;42(4):294‐303.
    pubmed: 20525046
  11. Karikoski NP, McGowan CM, Singer ER. Pathology of natural cases of equine endocrinopathic laminitis associated with hyperinsulinemia.. Vet Pathol 2015;52(5):945‐956.
    pubmed: 25232034
  12. Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA. Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light‐breed horses.. J Vet Intern Med 2019;33(3):1483‐1492.
    pmc: PMC6524466pubmed: 30912229
  13. de Laat MA, Clement CK, McGowan CM. Toll‐like receptor and pro‐inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: implications for laminitis.. Vet Immunol Immunopathol 2014;157(1–2):78‐86.
    pubmed: 24246153
  14. Cassimeris L, Engiles JB, Galantino‐Homer H. Interleukin‐17A pathway target genes are upregulated in equus caballus supporting limb laminitis.. PLoS One 2020;15(12):e0232920.
    pmc: PMC7728170pubmed: 33301461
  15. Gardner AK, van Eps AW, Watts MR, Burns TA, Belknap JK. A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse.. Vet J 2017;221:62‐67.
    pubmed: 28283083
  16. Obel N. Studies on the Histopathology of Acute Laminitis [Dissertation].. Uppsala, Sweden: Almqvist & Wiksell Boktryckeri; 1948.
  17. Lane HE, Burns TA, Hegedus OC. Lamellar events related to insulin‐like growth factor‐1 receptor signalling in two models relevant to endocrinopathic laminitis.. Equine Vet J 2017;49(5):643‐654.
    pubmed: 28078757
  18. Leise BS, Faleiros RR, Watts M. Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.. Equine Vet J 2011;43(1):54‐61.
    pubmed: 21143634
  19. van Eps AW, Burns TA. Are there shared mechanisms in the pathophysiology of different clinical forms of laminitis and what are the implications for prevention and treatment?. Vet Clin North Am Equine Pract 2019;35(2):379‐398.
    pubmed: 31126692
  20. Faleiros RR, Leise BS, Watts M, Johnson PJ, Black SJ, Belknap JK. Laminar chemokine mRNA concentrations in horses with carbohydrate overload‐induced laminitis.. Vet Immunol Immunopathol 2011;144(1–2):45‐51.
    pubmed: 21889804
  21. Leise BS, Watts M, Tanhoff E, Johnson PJ, Black SJ, Belknap JK. Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis.. J Vet Intern Med 2012;26(4):996‐1004.
    pubmed: 22805114
  22. Godman JD, Burns TA, Kelly CS. The effect of hypothermia on influx of leukocytes in the digital lamellae of horses with oligofructose‐induced laminitis.. Vet Immunol Immunopathol 2016;178(Oct 1):22‐28.
    pubmed: 27496739
  23. Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: implications for pasture‐associated laminitis.. Equine Vet J 2015;47(4):489‐493.
    pubmed: 24963607
  24. Belknap JK. The pharmacologic basis for the treatment of developmental and acute laminitis.. Vet Clin North Am Equine Pract 2010;26(1):115‐124.
    pubmed: 20381740
  25. Dern K, Burns TA, Watts MR, Eps AW, Belknap JK. Influence of digital hypothermia on lamellar events related to IL‐6/gp130 signalling in equine sepsis‐related laminitis.. Equine Vet J 2020;52(3):441‐448.
    pubmed: 31509270
  26. Lane H, Watts M, Geor R. Laminar growth factor‐related signaling in a model of equine metabolic syndrome (EMS) associated laminitis.. Paper presented at Proceedings of the 7th International Equine Conference on Laminitis and Diseases of the Foot: West Palm Beach, FL, Poster presentation; 2013.
  27. Blikslager AT, Yin C, Cochran AM, Wooten JG, Pettigrew A, Belknap JK. Cyclooxygenase expression in the early stages of equine laminitis: a cytologic study.. J Vet Intern Med 2006;20(5):1191‐1196.
    pubmed: 17063715
  28. Bharti R, Dey G, Mandal M. Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: a snapshot of IL‐6 mediated involvement.. Cancer Lett 2016;375(1):51‐61.
    pubmed: 26945971
  29. Tomlinson DC, Baxter EW, Loadman PM, Hull MA, Knowles MA. FGFR1‐induced epithelial to mesenchymal transition through MAPK/PLCgamma/COX‐2‐mediated mechanisms.. PLoS One 2012;7(6):e38972.
    pmc: PMC3373505pubmed: 22701738
  30. Neil JR, Johnson KM, Nemenoff RA, Schiemann WP. Cox‐2 inactivates smad signaling and enhances EMT stimulated by TGF‐beta through a PGE2‐dependent mechanisms.. Carcinogenesis 2008;29(11):2227‐2235.
    pmc: PMC2577139pubmed: 18725385
  31. Chattopadhyay I, Ambati R, Gundamaraju R. Exploring the crosstalk between inflammation and epithelial‐mesenchymal transition in cancer.. Mediators Inflamm 2021;2021:9918379.
    pmc: PMC8219436pubmed: 34220337
  32. Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial‐mesenchymal transition.. Cell 2020;9(1):217.
    doi: 10.3390/cells9010217pmc: PMC7017057pubmed: 31952344google scholar: lookup
  33. Markopoulos GS, Roupakia E, Marcu KB, Kolettas E. Epigenetic regulation of inflammatory cytokine‐induced epithelial‐to‐mesenchymal cell transition and cancer stem cell generation.. Cell 2019;8(10):1143.
    doi: 10.3390/cells8101143pmc: PMC6829508pubmed: 31557902google scholar: lookup
  34. Sud V, Abboud A, Tohme S, Vodovotz Y, Simmons RL, Tsung A. IL‐17A ‐ a regulator in acute inflammation: insights from in vitro, in vivo and in silico studies.. Cytokine 2021;139:154344.
    pubmed: 29954675
  35. Cassimeris L, Armstrong C, Burger QC, Stokes S, van Eps A, Galantino‐Homer H. Continuous digital hypothermia reduces expression of keratin 17 and 1L‐17A inflammatory pathway mediators in equine laminitis induced by hyperinsulinemia.. Vet Immunol Immunopathol 2021;241:110326.
    pubmed: 34562796
  36. Pan J, Fukuda K, Saito M. Mechanical stretch activates the JAK/STAT pathway in rat cardiomyocytes.. Circ Res 1999;84(10):1127‐1136.
    pubmed: 10347087
  37. Cittadini A, Monti MG, Iaccarino G. SOCS1 gene transfer accelerates the transition to heart failure through the inhibition of the gp130/JAK/STAT pathway.. Cardiovasc Res 2012;96(3):381‐390.
    pmc: PMC3732068pubmed: 22875468
  38. Machida T, Nishida K, Nasu Y. Inhibitory effect of JAK inhibitor on mechanical stress‐induced protease expression by human articular chondrocytes.. Inflamm Res 2017;66(11):999‐1009.
    pubmed: 28752178
  39. Yano S, Komine M, Fujimoto M, Okochi H, Tamaki K. Mechanical stretching in vitro regulates signal transduction pathways and cellular proliferation in human epidermal keratinocytes.. J Invest Dermatol 2004;122(3):783‐790.
    pubmed: 15086566
  40. Honsho S, Nishikawa S, Amano K. Pressure‐mediated hypertrophy and mechanical stretch induces IL‐1 release and subsequent IGF‐1 generation to maintain compensative hypertrophy by affecting AKT and JNK pathways.. Circ Res 2009;105(11):1149‐1158.
    pubmed: 19834007
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.