Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint

Abstract

BackgroundThe metacarpophalangeal joint undergoes enormous loading during locomotion and can therefore often become inflamed, potentially resulting in osteoarthritis (OA). There are studies indicating that the endocannabinoid system (ECS) modulates synovium homeostasis, and could be a promising target for OA therapy. Some cannabinoid receptors, which modulate proliferative and secretory responses in joint inflammation, have been functionally identified in human and animal synovial cells.ObjectiveTo characterize the cellular distribution of the cannabinoid receptors 1 (CB1R) and 2 (CB2R), and the cannabinoid-related receptors transient receptor potential vanilloid type 1 (TRPV1), G protein-related receptor 55 (GPR55) and peroxisome proliferator-activated receptor alpha (PPARα) in the synovial membrane of the metacarpophalangeal joint of the horse.AnimalsThe dorsal synovial membranes of 14 equine metacarpophalangeal joints were collected post-mortem from an abattoir.Materials and methodsThe dorsal synovial membranes of 14 equine metacarpophalangeal joints were collected post-mortem from an abattoir. The expression of the CB1R, CB2R, TRPV1, GPR55, and PPARα in synovial tissues was studied using qualitative and quantitative immunofluorescence, and quantitative real-time reverse transcriptase PCR (qRT-PCR). Macrophage-like (MLS) and fibroblast-like (FLS) synoviocytes were identified by means of antibodies directed against IBA1 and vimentin, respectively.ResultsBoth the mRNA and protein expression of the CB2R, TRPV1, GPR55, and PPARα were found in the synoviocytes and blood vessels of the metacarpophalangeal joints. The synoviocytes expressed the mRNA and protein of the CB1R in some of the horses investigated, but not in all.Conclusions and clinical importanceGiven the expression of the CB1R, CB2R, TRPV1, GPR55, and PPARα in the synovial elements of the metacarpophalangeal joint, these findings encouraged the development of new studies supporting the use of molecules acting on these receptors to reduce the inflammation during joint inflammation in the horse.

Improved quality of life and pain relief in mature horses with osteoarthritis after oral transmucosal cannabidiol oil administration as part of an analgesic regimen

“…The results of various studies have encouraged the development of new studies supporting the use of molecules acting on these receptors to reduce joint inflammation in horses. This research has provided an anatomical basis for further studies to explore the therapeutic use of non-psychotropic cannabinoids for pain management in horses (2,(42)(43)(44). Research in humans has shown that CBD reduces stress-related signals that can lead to chronic inflammation and pain responses (45).…”

Expression of Cannabinoid Receptors in the Trigeminal Ganglion of the Horse

“…Marker for macrophages-the goat anti-IBA1 antibody, recently used on horse tissue [12,14], was directed against a peptide with the sequence C-TGPPAKKAISELP, from the C Terminus of the porcine IBA1 sequence. Horse and porcine IBA1 molecules share 92.3% identity (https://www.uniprot.org/, accessed on 30 June 2019), and it is plausible that the antibody used can also recognise IBA1 in the horse.…”

“…There is existing evidence suggesting that cannabinoids may effectively alleviate neuropathic pain and hyperalgesia by inhibiting neuronal transmission in pain pathways [7,8]. Although there is a paucity of university-led research on cannabis therapy in equines, in recent years, some interesting studies have shown beneficial therapeutic effects of cannabinoid molecules in horses with allodynia [9], degenerative painful conditions such as osteoarthritis and laminitis [10,11], and also behavioral disturbances [12]. Consequently, considering the pronounced antinociceptive effects of cannabinoids, they could represent a promising therapeutic approach for the clinical management of TGM headshaking, should the appropriate receptors be expressed in the equine trigeminal ganglion.…”

Endocannabinoid System Receptors at the Hip and Stifle Joints of Middle-Aged Dogs: A Novel Target for the Therapeutic Use of Cannabis sativa Extract in Canine Arthropathies

“…In recent years, the endocannabinoid system (ECS) has materialised as a possible therapeutic target in veterinary medicine owing to its complicity in a plethora of physiological processes including pain, inflammation, immune function, neurological function, and body homeostasis [ 1 , 2 ]. The ECS consists of the endogenous cannabinoids N-arachidonylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), receptors, and enzymes which regulate the synthesis and degradation of endocannabinoids.…”

“…The ECS plays a crucial role in maintaining joint health and bone metabolism by modulating the activity of immune cells and reducing inflammation in both tissues, with evidence suggesting that it can regulate bone formation and resorption [ 24 , 25 ]. The mRNA and the immunoreactivity for the CB1R, CB2R, and GPR55 have already been described in the synovial membrane of the metacarpophalangeal joints of horses [ 1 ].…”