Bone Abstracts

Background: Cannabinoid receptors are expressed in synovial joints but their role in joint disease is unknown. Here we examined the role of the type 2 cannabinoid receptor (CB2) in the pathogenesis of age-related osteoarthritis and osteoarthritis caused by destabilisation of the medial meniscus (DMM) in WT and CB2-deficient mice (Cnr2^−/− mice).

Methods: The severity of arthritis was graded histologically according to standard techniques and differences between genotypes were compared by Student’s t-test

Results: Cartilage degeneration was (mean ±S.E.M.) 34%±10 more severe at the medial compartment of operated joints of Cnr2^−/− mice compared with WT littermates (P=0.009) and specifically 40%±13 more severe at the tibial plateau (P=0.012). There were no significant differences between Cnr2^−/− mice and WT in the microarchitecture of subchondral bone. Similar analyses of aged mice that developed spontaneous osteoarthritis revealed that arthritis in the medial compartment of Cnr2^−/− mice was 60%±14 more severe than WT littermates (P=0.004). Furthermore, treatment of young mice that underwent DMM and were administered with the CB2-selective agonist HU308 significantly inhibited progression of arthritis in the medial compartment of operated joints in WT mice with 32% less damage at the tibial plateau (P=0.019) and 18% less damage at the femoral condyle (P=0.029) compared with mice administered with vehicle. In contrast treatment with HU308 had no significant protective effect in Cnr2^−/− mice, indicating a CB2-mediated effect.

Conclusion: We conclude that CB2 receptor deficiency predisposes to age-related and surgically-induced osteoarthritis in mice and that CB2 agonists have protective effects. These findings suggest that further studies on the role of CB2 pathway in humans with osteoarthritis are warranted.