Distribution of endocannabinoid system receptors in the equine hoof: dysregulation as a potential therapeutic target for laminitis.
Abstract: A growing body of evidence indicates that the endocannabinoid system (ECS) is essential for controlling the homeostasis of the skin and that the ECS is modified in the presence of skin disease. It is plausible to expect that the lamellar junction of the hoof expresses cannabinoid receptors and that their expression could be affected by lamellar disease. The goal of this study was to characterise the cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the G protein-coupled receptor 55 (GPR55) within the dermo-epidermal junction of the hooves of healthy and laminitic horses. The expression of the CB1R, CB2R, and GPR55 within the dermo-epidermal lamellar junction of six healthy and 12 laminitic hooves was studied using polymerase chain reaction (PCR) and immunofluorescence. Both the mRNA and protein expression of the CB1R, CB2R, and GPR55 were found in the dermo-epidermal lamellar junction of horse hooves. The immunolabelling was expressed by the epithelial cells of the primary and secondary laminae of healthy hooves (CB2R > GPR55 > CB1R). The presence of CB1R, CB2R, and GPR55 immunoreactivity in the healthy laminar epithelial cells, coupled with increased protein expression in pathological epithelial cells, provided strong motivation for future investigation. These findings suggest that cannabinoid compounds which interact with these receptors may influence lamellar healing and mitigate inflammation in hoof diseases, particularly laminitis.
© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Publication Date: 2025-07-01 PubMed ID: 40593311PubMed Central: 7023045DOI: 10.1007/s00418-025-02397-yGoogle Scholar: Lookup
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Summary
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The study analyzes the presence and potential role of endocannabinoid system (ECS) receptors in the hoof health of horses, particularly in connection with a disease called laminitis. It suggests that targeting these receptors could provide therapeutic relief for horses suffering from the disease.
Research Objectives and Methods
- This research aimed at examining cannabinoids, specifically cannabinoid receptor type 1 (CB1R), type 2 (CB2R), and G protein-coupled receptor 55 (GPR55) in the dermo-epidermal junction, the interface between the outermost layer of the skin and the underlying tissue, of the hooves of healthy and laminitic horses.
- Using polymerase chain reaction (PCR) and immunofluorescence, technologies that allow scientists to replicate and visualize specific DNA sequences, the researchers studied the expression of these cannabinoid receptors in six healthy horse hooves and 12 laminitic ones.
Findings
- Both the mRNA and protein expression of the CB1R, CB2R and GPR55 were found at the dermo-epidermal lamellar junction of the horse hooves. Immunolabelling, a technique that uses antibodies to detect specific antigens, showed the presence of these receptors in the epithelial cells (the cells that cover the outside of the body and line organs and cavities within the body) of the primary and secondary laminae of healthy hooves.
- There was more of the CB2R receptor than GPR55 or CB1R in the healthy hooves. Interestingly, there was an increased expression of these receptors in pathological or disease-affected cells.
Implications and Future Scope
- The findings of this research suggest that the endocannabinoid system could play a significant role in hoof health and disease. The detection of CB1R, CB2R, and GPR55 immunoreactivity – how reactive the system is to these receptors – in the healthy laminar epithelial cells and increased expression in pathological cells hints at this potential.
- These increases provide a compelling reason to continue exploring how cannabis-derived compounds that interact with these receptors could influence the healing of lamellar tissues and reduce inflammation in hoof diseases, particularly laminitis.
Cite This Article
APA
Zamith Cunha R, Gobbo F, Morini M, Zannoni A, Mainardi C, D'arpe L, Gramenzi A, Chiocchetti R.
(2025).
Distribution of endocannabinoid system receptors in the equine hoof: dysregulation as a potential therapeutic target for laminitis.
Histochem Cell Biol, 163(1), 71.
https://doi.org/10.1007/s00418-025-02397-y Publication
Researcher Affiliations
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy. rodrigo.zamithcunha@studio.unibo.it.
- Department of Veterinary Medicine, University of Teramo, Teramo, Italy. rodrigo.zamithcunha@studio.unibo.it.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medicine, University of Teramo, Teramo, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
MeSH Terms
- Animals
- Horses
- Hoof and Claw / metabolism
- Hoof and Claw / pathology
- Receptors, Cannabinoid / metabolism
- Receptors, Cannabinoid / genetics
- Receptors, Cannabinoid / analysis
- Inflammation / metabolism
- Inflammation / drug therapy
- Horse Diseases / metabolism
- Horse Diseases / drug therapy
- Horse Diseases / pathology
- Endocannabinoids / metabolism
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Receptor, Cannabinoid, CB2 / metabolism
- Receptor, Cannabinoid, CB2 / genetics
- Receptor, Cannabinoid, CB1 / metabolism
- Receptor, Cannabinoid, CB1 / genetics
Conflict of Interest Statement
Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval and consent to participate: According to Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 regarding the protection of animals used for scientific purposes, Italian legislation (D. Lgs. n. 26/2014) did not require any approval by competent authorities or ethics committees as this study did not influence any therapeutic decisions. Consent for publication: All the authors have approved the publication of this manuscript.
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