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Fraxinellone Attenuates Rheumatoid Inflammation in Mice

 Seung Min Jung  ;  Jaeseon Lee  ;  Seung Ye Baek  ;  Juhyun Lee  ;  Se Gwang Jang  ;  Seung-Min Hong  ;  Jin-Sil Park  ;  Mi-La Cho  ;  Sung-Hwan Park  ;  Seung-Ki Kwok 
 International Journal of Molecular Sciences, Vol.19(3) : E829, 2018 
Journal Title
 International Journal of Molecular Sciences 
Issue Date
collagen-induced arthritis ; fraxinellone ; inflammatory arthritis ; osteoclastogenesis ; rheumatoid arthritis
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Jung, Seung Min (정승민) ORCID logo https://orcid.org/0000-0003-3465-2181
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