PMID- 25115332
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20220330
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 15
DP  - 2014 Aug 12
TI  - Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis.
PG  - 275
LID - 10.1186/1471-2474-15-275 [doi]
LID - 275
AB  - 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-gamma 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-alpha-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.
FAU - Fukuda, Shin
AU  - Fukuda S
FAU - Kohsaka, Hitoshi
AU  - Kohsaka H
FAU - Takayasu, Aiko
AU  - Takayasu A
FAU - Yokoyama, Waka
AU  - Yokoyama W
FAU - Miyabe, Chie
AU  - Miyabe C
FAU - Miyabe, Yoshishige
AU  - Miyabe Y
FAU - Harigai, Masayoshi
AU  - Harigai M
FAU - Miyasaka, Nobuyuki
AU  - Miyasaka N
FAU - Nanki, Toshihiro
AU  - Nanki T
AD  - Department of Medicine and Rheumatology, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, 113-8519 
      Bunkyo-ku, Tokyo, Japan. nanki@med.teikyo-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140812
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (CNR2 protein, human)
RN  - 0 (Cannabinoids)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - TDG8048RDA (1,1-dimethylbutyl-1-deoxy-Delta(9)-THC)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Arthritis, Rheumatoid/drug therapy/*metabolism
MH  - Cannabinoids/*administration & dosage
MH  - Cells, Cultured
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Middle Aged
MH  - Receptor, Cannabinoid, CB2/*agonists/*biosynthesis
MH  - Synovial Membrane/drug effects/metabolism
PMC - PMC4243420
EDAT- 2014/08/15 06:00
MHDA- 2015/05/13 06:00
PMCR- 2014/08/12
CRDT- 2014/08/14 06:00
PHST- 2013/12/12 00:00 [received]
PHST- 2014/08/07 00:00 [accepted]
PHST- 2014/08/14 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
PHST- 2014/08/12 00:00 [pmc-release]
AID - 1471-2474-15-275 [pii]
AID - 2224 [pii]
AID - 10.1186/1471-2474-15-275 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2014 Aug 12;15:275. doi: 10.1186/1471-2474-15-275.