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Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis
Open accessAbstract
BACKGROUND: Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB(2)) is expressed primarily by immune cells. Theoretically, selective CB(2) agonists should be devoid of psychoactive effects. In this study, we investigated therapeutic effects of a selective CB(2) agonist on arthritis. METHODS: The expression of CB(2) was analyzed with immunohistochemistry and Western blotting. Interleukin (IL)-6, matrix metalloproteinase-3 (MMP-3), and chemokine (C-C motif) ligand 2 (CCL2) were quantified with enzyme-linked immunosorbent assays (ELISA). Osteoclastogenesis was assessed with tartrate-resistant acid phosphatase staining and the resorption of coated-calcium phosphate. Effect of JWH133, a selective CB(2) agonist, on murine collagen type II (CII)-induced arthritis (CIA) was evaluated with arthritis score, and histological and radiographic changes. IFN-γ and IL-17 production by CII-stimulated splenocytes and serum anti-CII Ab were analyzed by ELISA. RESULTS: Immunohistochemistry showed that CB(2) was expressed more in the synovial tissues from the rheumatoid joints than in those from the osteoarthritis joints. CB(2) expression on RA FLS was confirmed with Western blot analysis. JWH133 inhibited IL-6, MMP-3, and CCL2 production from tumor necrosis factor-α-stimulated fibroblast-like synoviocytes (FLS) derived from the rheumatoid joints, and osteoclastogenesis of peripheral blood monocytes. Administration of JWH133 to CIA mice reduced the arthritis score, inflammatory cell infiltration, bone destruction, and anti-CII IgG1 production. CONCLUSION: The present study suggests that a selective CB(2) agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis.
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Within rheumatoid arthritis synovial tissue, CB2 receptors are expressed on macrophages, CD4+ T cells, CD8+ T cells, and B cells.
“Within rheumatoid arthritis synovial tissue, CB 2 receptors are expressed on macrophages, CD4 + T cells, CD8 + T cells, and B cells (Fukuda et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Fukuda et al, 2014
The selective CB2 receptor agonists HU-308 and JWH133 reduce IL-6, IL-8, and matrix metalloproteinases-3 from TNFα or IL-1β stimulated rheumatoid arthritis and osteoarthritis fibroblast-like synoviocytes.
“The selective CB 2 receptor agonists HU-308 and JWH133 also reduce IL-6, IL-8, and matrix metalloproteinases-3 from TNFα or IL-1β stimulated rheumatoid arthritis and osteoarthritis FLS (Fukuda et al, 2014;Gui et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Fukuda et al, 2014
The selective CB2 receptor agonists JWH133 and HU-308 attenuate paw swelling, cartilage degradation, and bone erosion in mice subjected to CIA.
“The selective CB 2 receptor agonists JWH133 and HU-308 attenuated paw swelling, cartilage degradation, and bone erosion in mice subjected to CIA (Fukuda et al, 2014;Gui et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Fukuda et al, 2014
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Metadata
- Authors
- Fukuda, S., Kohsaka, H., Takayasu, A., Yokoyama, W., Miyabe, C., Miyabe, Y., Harigai, M., Miyasaka, N., & Nanki, T.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Nanki, Toshihiro
- Venue
- BMC Musculoskeletal Disorders
- Published
- 2014-08-12
- Volume
- 15
- Issue
- 1
- Pages
- 275-275
- ISSN
- 1471-2474 (ISSN-L)
- PMC
- PMC4243420
- OpenAlex
- W2069356506
- Cited by
- 93
- References
- 40
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 8 · 2018: 13 · 2017: 10 · 2016: 7 · 2015: 3 · 2014: 3
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Musculoskeletal Disorders (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Tokyo Medical and Dental University
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- CB2 receptor, CB2 receptor agonist, JWH-133, rheumatoid arthritis, synovial fibroblasts, osteoclastogenesis, collagen-induced arthritis, interleukin-6, MMP-3, MCP-1, synovium, bone destruction, anti-collagen type II antibodies, immunosuppressive therapy
- MeSH terms
- Adult, Aged, Animals, Arthritis, Rheumatoid, Cannabinoids, Cells, Cultured, Humans, Male, Mice, Inbred DBA, Middle Aged, Synovial Membrane, Drug Delivery Systems, Receptor, Cannabinoid, CB2, Mice
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