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J Bone Miner Res. 2018 Dec 3. doi: 10.1002/jbmr.3637. [Epub ahead of print]

Cannabinoid receptor 2 agonist prevents local and systemic inflammatory bone destruction in rheumatoid arthritis.

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Department of Radiology, The First Affiliated Hospital of Soochow University.
Department of Orthopedics, The First Affiliated Hospital of Soochow University.
Orthopedics Institute, Soochow University.


Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the non-inflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro-inflammatory M1-like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, IL-1β, and IL-6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor-κB (NF-κB) ligand (RANKL), matrix metallopeptidase-9, tartrate-resistant acid phosphatase, cathepsin K, and nuclear factor of activated T-cells 1 in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL-induced NF-κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. This article is protected by copyright. All rights reserved.


NF-κB signaling pathway; bone destruction; cannabinoid receptor 2; inflammation; rheumatoid arthritis


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