Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis

Background: Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid receptors (CB) are now considered to be promising therapeutic targets in human rheumatology for pain and inflammation, however little is known about the equine endocannabinoid system.

Objectives: 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.

Study design: 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. Co-localised synovial sections were also immunostained with antibodies to CB1 and CB2. Five regions of interest (ROIs) were randomly selected from digital images of manually segmented synovial intima and scored blindly for positive cellular immunoreactive staining by 2 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.

Main limitations: 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. This article is protected by copyright. All rights reserved.