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Frontiers in veterinary science2025; 12; 1723160; doi: 10.3389/fvets.2025.1723160

Cannabinoid and cannabinoid related receptors in fibroblasts, inflammatory and endothelial cells of the equine hoof with and without laminitis: novel pharmacological target.

Abstract: Evidence suggests that the endocannabinoid system (ECS) is crucial for regulating inflammation, cell proliferation and pain. The ECS is composed of cannabinoid receptors such as type 1 (CBR1), type 2 (CBR2) and GPR55, endocannabinoids and enzymes. Proteins of ECS have previously been localized in the epidermal cells of the horse hooves. Given the physio-pathological role and cellular distribution of the ECS across species, the authors hypothesized that cannabinoid receptors are expressed within the inflammatory cells, fibroblasts and endothelial cells of the equine hoof laminae, going beyond the epidermal cells. Unassigned: To preliminary analyze the gene expression of Cn1r, Cn2r and GPR55 in the hoof laminae and test the specificity of the antibody against GPR55. To characterize the distribution and expression of CBRs in the inflammatory cells and fibroblasts of the laminar junction of equine healthy hooves and with laminitis. Unassigned: Animals were divided into 3 groups: healthy, acute laminitis and chronic laminitis. A total of 18 samples were collected and processed from the front limb of animals slaughtered for consumption or euthanized (6 control animals, 4 acute laminitis, 8 chronic laminitis). Unassigned: Analysis of CBR1, CBR2 and GPR55 protein expression was made by fluorescence microscopy with co-localization with antibodies against the macrophages marker IBA1, the T cell marker CD3, the neutrophils marker calprotectin (MAC387), the fibroblasts marker vimentin (Clove V9) and the nerve fibers marker Substance P. Preliminary analysis was performed to evaluate gene expression (, , and ) using real-time PCR and to verify the specificity of the primary antibody (Gpr55) with Western Blotting (WB). Unassigned: The resident pool of inflammatory cells in the normal laminae and the inflammatory infiltrate cells of the affected equine laminae showed protein expression of CB2R and GPR55; no CB1R staining was seen at the inflammatory cells. Equine dermal fibroblast and endothelial cells exhibited protein expressions of CB1R, CBR2 and GPR55. Substance P positive nerve fibers were positive for CB1R. Unassigned: Cannabinoid receptors are expressed in different immune cell types of the hoof laminae, pointing to the role of the ECS in modulating inflammatory outburst, tissue degeneration and pain. Our results serve as a foundation for the development of new veterinary pharmacotherapies that target the ECS during laminitis.
Copyright © 2025 Zamith Cunha, Gobbo, Morini, Salamanca, Zanoni, Bernardini, Gramenzi and Chiocchetti.
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Publication Date: 2025-11-28 PubMed ID: 41394912PubMed Central: PMC12699270DOI: 10.3389/fvets.2025.1723160Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This study investigates the presence and distribution of cannabinoid receptors in various cell types of the equine hoof, both healthy and affected by laminitis, to explore their potential as targets for new treatments.
  • The research focuses on cannabinoid receptors CB1R, CB2R, and GPR55 in inflammatory cells, fibroblasts, and endothelial cells within the hoof’s laminar tissue.

Introduction and Background

  • The endocannabinoid system (ECS) regulates inflammation, cell growth, and pain and includes cannabinoid receptors CB1R, CB2R, and GPR55, along with endogenous cannabinoids and enzymes.
  • Previous studies localized ECS proteins mainly in epidermal cells of horse hooves, but their presence in other cell types within hoof tissues had not been well characterized.
  • Given that laminitis involves inflammation and tissue degeneration in the hoof, understanding cannabinoid receptor expression could highlight novel pharmacological targets.

Objectives

  • Preliminarily analyze gene expression of the cannabinoid receptors (CB1R, CB2R, GPR55) in the laminar tissue of equine hooves using real-time PCR.
  • Test the specificity of antibodies targeting GPR55 via Western Blotting.
  • Characterize and map the protein expression of the three cannabinoid receptors in inflammatory cells, fibroblasts, and endothelial cells in both healthy and laminitic hooves using fluorescence microscopy.

Methods

  • Sample Collection:
    • 18 total samples from the front limbs of horses divided into groups: 6 healthy controls, 4 with acute laminitis, and 8 with chronic laminitis.
    • Samples obtained post-mortem from slaughtered or euthanized animals.
  • Immunofluorescence:
    • Used antibodies to detect CB1R, CB2R, and GPR55 protein expression.
    • Co-staining was performed with markers:
      • IBA1 for macrophages
      • CD3 for T cells
      • Calprotectin (MAC387) for neutrophils
      • Vimentin (Clove V9) for fibroblasts
      • Substance P for nerve fibers
  • Gene expression analysis employed real-time PCR for cannabinoid receptor genes.
  • Western Blotting confirmed the specificity of GPR55 antibodies.

Key Findings

  • Inflammatory Cells:
    • Macrophages, T cells, and neutrophils within the laminae expressed CB2R and GPR55.
    • No CB1R expression was detected in inflammatory cells.
  • Fibroblasts and Endothelial Cells:
    • Both expressed CB1R, CB2R, and GPR55 proteins.
  • Nerve Fibers:
    • Substance P-positive nerve fibers were positive for CB1R, which may relate to pain signaling pathways.

Interpretation and Significance

  • The presence of CB2R and GPR55 in immune cells implicates cannabinoid receptors in modulating inflammatory responses within the hoof, important for laminitis pathology.
  • Expression of all three receptors (CB1R, CB2R, GPR55) in fibroblasts and endothelial cells suggests the ECS could influence tissue remodeling and vascular function during laminitis.
  • The localization of CB1R in nerve fibers linked to pain transmission highlights the ECS’s potential role in managing laminitis-associated pain.
  • These findings establish a biological basis for developing therapies targeting cannabinoid receptors to control inflammation, reduce tissue damage, and alleviate pain in equine laminitis.

Conclusion

  • This research identifies cannabinoid receptors in diverse cell types related to inflammation and structural changes in both healthy and laminitic equine hooves, extending knowledge beyond previous epidermal studies.
  • The ECS represents a promising pharmacological target that could lead to innovative veterinary treatments for laminitis by modulating inflammation, tissue degeneration, and pain.

Cite This Article

APA
Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R. (2025). Cannabinoid and cannabinoid related receptors in fibroblasts, inflammatory and endothelial cells of the equine hoof with and without laminitis: novel pharmacological target. Front Vet Sci, 12, 1723160. https://doi.org/10.3389/fvets.2025.1723160

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 12
Pages: 1723160
PII: 1723160

Researcher Affiliations

Zamith Cunha, Rodrigo
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
  • Department of Veterinary Medicine, University of Teramo, Teramo, Italy.
Gobbo, Francesca
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Morini, Maria
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Salamanca, Giulia
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
  • Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy.
Zanoni, Augusta
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Bernardini, Chiara
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Gramenzi, Alessandro
  • Department of Veterinary Medicine, University of Teramo, Teramo, Italy.
Chiocchetti, Roberto
  • Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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