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Equine veterinary journal2022; 55(4); 681-695; doi: 10.1111/evj.13860

Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis.

Abstract: Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid (CB) receptors are now considered to be promising therapeutic targets in human rheumatology for pain and inflammation, however, little is known about the equine endocannabinoid system. Objective: The primary goal was to assess the presence and expression pattern of CB1 and CB2 in the synovium of healthy joints. A secondary goal was to explore the relationship between the CB expression, degree of synovitis and OA pathology. Methods: Ex vivo experimental study. Methods: Metacarpophalangeal joints (n = 25) from a tissue bank were studied. The joints were dissected, and the articular cartilage lesions were scored. Synovial membrane specimens (n = 45) were harvested, fixed and the degree of synovitis was graded on histological sections. Colocalised synovial sections were also immunostained with antibodies to CB1 and CB2. Five regions of interest were randomly selected from digital images of manually segmented synovial intima and scored blindly for positive cellular immunoreactive staining by two independent observers. Interobserver agreement was calculated with an intraclass correlation coefficient (ICC). Relationships between CB1 and CB2 immunoreactive scores and synovitis or joint OA grade were explored with mixed linear models. Results: CB1 was expressed in synovial intimal cells in all specimens studied whereas CB2 expression was identified in 94%. Both receptors were also expressed in the subintimal blood vessel walls. ICCs were 84.6% (CB1) and 92.9% (CB2) for the immunoreactivity scores. Both CB1 and CB2 expression were significantly upregulated (p = 0.04 and p = 0.03, respectively) with increasing degree of synovitis. Conversely, CB1 expression significantly decreased (p = 0.03) with increasing severity of OA. Conclusions: The type of synovial cell expressing CB1 or CB2 was not investigated. Conclusions: Equine synovial intimal cells constitutively express both CB1 and CB2 receptors that are upregulated with synovitis and may have a role in joint pain. They are potential targets for therapy with cannabinoid molecules or their derivatives. Unassigned: Osteoarthritis (OA) ist eine Hauptursache equiner Lahmheit. Cannabinoid-Rezeptoren (CB) werden inzwischen als vielversprechendes Behandlungsziel von Schmerz und Inflammation in humaner Rheumatologie angesehen, indessen ist wenig über das equine Endocannabinoidsystem bekannt. Unassigned: Das Hauptziel der Studie war die Feststellung der Anwesenheit und Expressionsmuster von CB1 und CB2 im Synovium gesunder Gelenke. Sekundärziel war die Untersuchung des Verhältnisses zwischen CB-Expression, Grad von Synovitis und OA Pathologie. Methods: Ex vivo Experimentalstudie. Methods: Zehengrundgelenke (n = 25) einer Gewebebank wurden untersucht. Die Gelenke wurden seziert und Gelenkknorpelschäden bewertet. Proben von Synovialmembran (n = 45) wurden gesammelt, fixiert und der Grad von Synovitis wurde mithilfe histologischer Sektionen beurteilt. Co-lokalisierte Synovialabschnitte wurden außerdem immunhistochemisch gefärbt mit Antikörpern gegen CB1 und CB2. Fünf Regionen von Interesse (ROIs) wurden zufällig von digitalen Bildern manuell segmentierter synovialer Intima ausgewählt und von 2 unabhängigen, geblindeten Beobachtern auf positive zelluläre immunreaktive Färbung bewertet. Die Interobserver Übereinstimmung wurde kalkuliert mithilfe eines Intraklassenkorrelationskoeffizienten (ICC). Zusammenhänge zwischen CB1 und CB2 immunreaktiven Scores und Synovitis oder Grad der Gelenk OA wurden mithilfe linearer gemischter Modelle untersucht. Unassigned: CB1 wurde in synovialen Intimazellen aller untersuchten Proben exprimiert, wohingegen CB2-Expression in 94% identifiziert wurde. Beide Rezeptoren wurden ebenfalls in subintimalen Blutgefäßwänden exprimiert. ICCs waren 84.6% (CB1) und 92.9% (CB2) für die immunreaktiven Scores. Sowohl CB1- als auch CB2-Expression waren signifikant hochreguliert (P = 0.038 beziehungsweise P = 0.027) bei erhöhtem Grad der Synovitis. Hingegen verringerte sich die CB1-Expression signifikant (P = 0.03) mit steigendem Ausmaß von OA. HAUPTEINSCHRÄNKUNGEN: Der Typus synovialer Zellen, welche CB1 oder CB2 exprimierten, wurde nicht untersucht. Unassigned: Equine synoviale Intimazellen exprimieren konstitutiv sowohl CB1- als auch CB2-Rezeptoren, welche bei Synovitis hochreguliert werden und eine Rolle bei Gelenkschmerz spielen könnten. Sie sind potenzielle Ziele für die Therapie mit cannabinoiden Molekülen oder deren Derivate.
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Publication Date: 2022-08-13 PubMed ID: 35836386DOI: 10.1111/evj.13860Google Scholar: Lookup
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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 talks about the expression of cannabinoid receptors in the synovial membrane of healthy horses, its up-regulation in synovitis, and its potential role as a therapeutic target for joint ailments in horses.

Objectives and Methods

  • The study’s primary aim was to identify the existence and expression patterns of cannabinoid (CB) receptors, namely CB1 and CB2, in the synovial membrane (inner layer of the joint capsule) of healthy equine joints.
  • The secondary objective was to correlate CB expression levels with the degree of synovitis (inflammation of the synovial membrane) and OA (osteoarthritis) pathology.
  • The research was an ex vivo experimental study that involved 25 metacarpophalangeal joint specimens obtained from a tissue bank.
  • The joints were dissected, and any lesions in the articular cartilage were scored.
  • From these joints, 45 synovial membrane specimens were gathered, fixed, and the severity of synovitis was evaluated based on their histological sections.
  • These histological sections were also stained with antibodies specific to CB1 and CB2 to assess their expression.
  • Data on CB expression were analyzed blindly by two independent observers, and interobserver agreement was assessed with an intraclass correlation coefficient (ICC).
  • The relationship between CB1 and CB2 expression levels and the severity of synovitis or joint OA was evaluated using mixed linear models.

Results and Conclusions

  • Cannabinoid receptor CB1 was found to be expressed in synovial intimal cells (innermost cell layer of the synovium) in all specimens, while CB2 expression was detected in 94% of the specimens.
  • Both CB1 and CB2 were also expressed in the walls of the subintimal blood vessels.
  • The ICCs for CB1 and CB2 were 84.6% and 92.9% respectively, suggesting a high degree of agreement between observers in CB expression scoring.
  • Both CB1 and CB2 expression levels were found to increase with the increasing degree of synovitis, suggesting their upregulation may be involved in the inflammatory response in joint disease.
  • Interestingly, CB1 expression levels decreased with the severity of OA, indicating a potential protective role against cartilage degradation.
  • The study did not investigate which specific synovial cell types were expressing CB1 or CB2.
  • The findings from this study suggest that equine synovial intimal cells may have a constitutive role in expressing both CB1 and CB2 receptors, which become upregulated in the event of joint inflammation and could play a role in mitigating joint pain.
  • Therefore, these receptors may provide potential therapeutic targets for treating joint disorders in horses with cannabinoids or their derivatives.

Cite This Article

APA
Miagkoff L, Girard CA, St-Jean G, Richard H, Beauchamp G, Laverty S. (2022). Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis. Equine Vet J, 55(4), 681-695. https://doi.org/10.1111/evj.13860

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 4
Pages: 681-695

Researcher Affiliations

Miagkoff, Ludovic
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.
Girard, Christiane A
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.
St-Jean, Guillaume
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.
Richard, Hélène
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.
Beauchamp, Guy
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.
Laverty, Sheila
  • Comparative Orthopedic Research Laboratory, Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Q, Canada.

MeSH Terms

  • Animals
  • Horses
  • Humans
  • Receptors, Cannabinoid / metabolism
  • Synovial Membrane
  • Synovitis / veterinary
  • Synovitis / pathology
  • Osteoarthritis / veterinary
  • Cannabinoids / metabolism
  • Horse Diseases / pathology

Grant Funding

  • CF00142067 / Natural Sciences and Engineering Research Council of Canada
  • DF1_130184 / Quebec Cell, Tissue and Gene Therapy Network - ThéCell (a thematic network supported by the Fonds de recherche du Québec-Santé)
  • Santé Équine de la Faculté de Médecine Vétérinaire de l'Université de Montréal et Zoetis

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Citations

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