Activating a cannaboinoid receptor found to prevent inflammatory bone destruction in patients with rheumatoid arthritis

Researchers from The First Affiliated Hospital of Soochow University in China investigated the potential of a cannabinoid receptor 2 (CB2) agonist in preventing bone destruction and inflammation associated with collagen-induced arthritis (CIA) in mice. Their findings were published in the Journal of Bone and Mineral Research.

• CB2 has been implicated as an important clinical regulator of inflammation and malignant osteolysis.
• The researchers found that CB2 expression in markedly higher in CIA mice synovium and bone tissues than in non-inflamed synovium and bone tissues.
• Treatment with the CB2 selective agonist, JWH133, but not the antagonist, SR144528, suppressed CIA in mice without toxic effects. This was evidenced by the decrease in synovial hyperplasia, inflammatory responses, cartilage damage and periarticular and systemic bone destruction.
• JWH133 treatment also decreased the infiltration of pro-inflammatory M1-like macrophages and re-polarized macrophages from the M1 to M2 phenotype.
• In addition, JWH133 attenuated osteoclast formation and bone resorption, and reduced the expression of receptor activators of nuclear factor-kB (NF-kB) ligand (RANKL), matrix metallopeptidase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) and nuclear factor of activated T-cells 1 (NFAT-1) in CIA mice and osteoclast precursors.
• Mechanistically, JWH133 inhibited RANKL-induced NF-kB activation in the osteoclast precursors.
• Meanwhile, CB2 activation increased the expression of the anti-inflammatory protein interleukin (IL)-10 and reduced the expression of pro-inflammatory signaling molecules, such as tumor necrosis factor-a (TNF-a), IL-1B and IL-6.

Based on these findings, the researchers concluded that JWH133 ameliorates bone destruction in CIA mice by inhibiting the generation of osteoclasts and modulating inflammatory responses. This mechanism of action highlights its potential in the treatment of rheumatoid arthritis.

Journal Reference:

Zhu M, Yu B, Bai J, Wang X, Guo X, Liu Y, Lin J, Hu S, Zhang W, Tao Y, et al. CANNABINOID RECEPTOR 2 AGONIST PREVENTS LOCAL AND SYSTEMIC INFLAMMATORY BONE DESTRUCTION IN RHEUMATOID ARTHRITIS. Journal of Bone and Mineral Research. 2019;34(4):739–751. DOI: 10.1002/jbmr.3637