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Int J Mol Sci. 2018 Mar 13;19(3). pii: E829. doi: 10.3390/ijms19030829.

Fraxinellone Attenuates Rheumatoid Inflammation in Mice.

Author information

1
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 15-1 Yonseo-ro, Seodaemun-gu, Seoul 03722, Korea. jsmin00@yuhs.ac.
2
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. llooo@naver.com.
3
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. syeee23@catholic.ac.kr.
4
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. um26sw@hanmail.net.
5
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. yourelite@naver.com.
6
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. dkask0809@naver.com.
7
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. wlstlf81@catholic.ac.kr.
8
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. iammila@catholic.ac.kr.
9
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. rapark@catholic.ac.kr.
10
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. rapark@catholic.ac.kr.
11
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. seungki73@catholic.ac.kr.
12
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. seungki73@catholic.ac.kr.

Abstract

This study aimed to evaluate the therapeutic effect of fraxinellone on inflammatory arthritis and identify the underlying mechanisms. Fraxinellone (7.5 mg/kg) or a vehicle control was injected into mice with collagen-induced arthritis (CIA). The severity of arthritis was evaluated clinically and histologically. The differentiation of CD4⁺ T cells and CD19⁺ B cells was investigated in the presence of fraxinellone. Osteoclastogenesis after fraxinellone treatment was evaluated by staining with tartrate-resistant acid phosphatase (TRAP) and by measuring the mRNA levels of osteoclastogenesis-related genes. Fraxinellone attenuated the clinical and histologic features of inflammatory arthritis in CIA mice. Fraxinellone suppressed the production of interleukin-17 and the expression of RAR-related orphan receptor γ t and phospho-signal transducer and activator of transcription 3 in CD4⁺ T cells. CD19⁺ B cells showed lower expression of activation-induced cytidine deaminase and B lymphocyte-induced maturation protein-1 after treatment with fraxinellone. The formation of TRAP-positive cells and the expression of osteoclastogenesis-related markers were reduced in the presence of fraxinellone. Inhibition of interleukin-17 and osteoclastogenesis was also observed in experiments using human peripheral mononuclear cells. Fraxinellone alleviated synovial inflammation and osteoclastogenesis in mice. The therapeutic effect of fraxinellone was associated with the inhibition of cellular differentiation and activation. The data suggests that fraxinellone could be a novel treatment for inflammatory arthritis, including rheumatoid arthritis.

KEYWORDS:

collagen-induced arthritis; fraxinellone; inflammatory arthritis; osteoclastogenesis; rheumatoid arthritis

PMID:
29533969
PMCID:
PMC5877690
DOI:
10.3390/ijms19030829
[Indexed for MEDLINE]
Free PMC Article

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