Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid receptors (CB) are promising therapeutic targets in human rheumatology for pain and inflammation. However, scientists know very little about the equine endocannabinoid system. The primary aim of this ex vivo experimental study was to assess the presence and expression pattern of CB1 and CB2 receptors in the synovium of healthy joints. A secondary aim was to explore the relationship between the cannabinoid receptors expression, degree of synovitis and OA pathology.
Researchers studied metacarpophalangeal joints (n=25) from a tissue bank. They dissected the joints and scored the articular cartilage lesions. Then, they harvested and fixed synovial membrane specimens (n=45) and graded the degree of synovitis on histological sections. They immunostained co-localised synovial sections with antibodies to CB1 and CB2. The study randomly relected five regions of interest (ROIs) from digital images of manually segmented synovial intima. Two independent observers scored these regions blindly for positive cellular immunoreactive staining. The study calculated interobserver agreement with an intraclass correlation coefficient. Researchers explored the relationships between CB1 and CB2 immunoreactive scores and synovitis or joint OA grade.
The researchers identified CB1 expression in synovial intimal cells in all specimens studied. They identified CB2 expression in 94%. Both receptors were also expressed in the subintimal blood vessel walls. Interobserver agreements 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 degrees of synovitis. Conversely, CB1 expression significantly decreased (p=0.03) with increasing severity of OA.
Equine synovial intimal cells constitutively express both CB1 and CB2 receptors. These receptors are upregulated with synovitis. These receptors may have a role in joint pain. They are potential targets for therapy with cannabinoid molecules or their derivatives.