Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis

ABSTRACT 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 noninflamed synovium and...

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Published in:Journal of bone and mineral research Vol. 34; no. 4; pp. 739 - 751
Main Authors: Zhu, Mo, Yu, Binqin, Bai, Jiaxiang, Wang, Ximing, Guo, Xiaobin, Liu, Yu, Lin, Jiayi, Hu, Su, Zhang, Wen, Tao, Yunxia, Hu, Chunhong, Yang, Huilin, Xu, Yaozeng, Geng, Dechun
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-04-2019
Subjects:
Acid phosphatase
Acid phosphatase (tartrate-resistant)
Agonists
BONE DESTRUCTION
Bone growth
Bone resorption
Cannabinoid CB2 receptors
CANNABINOID RECEPTOR 2
Cartilage
Cathepsin K
Cell activation
Collagen
Hyperplasia
INFLAMMATION
Macrophages
Metalloproteinase
Metastases
NF-AT protein
NF‐κB SIGNALING PATHWAY
Osteoclastogenesis
Osteoclasts
Osteolysis
Osteoprogenitor cells
Phenotypes
RHEUMATOID ARTHRITIS
Synovium
TRANCE protein
Tumor necrosis factor
Tumor necrosis factor-TNF
RHEUMATOID ARTHRITIS
CANNABINOID RECEPTOR 2
NF-κB SIGNALING PATHWAY
INFLAMMATION
BONE DESTRUCTION
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Summary:ABSTRACT 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 noninflamed 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 (TNF‐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 (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, 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. © 2018 American Society for Bone and Mineral Research.
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ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.3637