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2018 ; 19
(3
): ä Nephropedia Template TP
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Fraxinellone Attenuates Rheumatoid Inflammation in Mice
#MMPMID29533969
Jung SM
; Lee J
; Baek SY
; Lee J
; Jang SG
; Hong SM
; Park JS
; Cho ML
; Park SH
; Kwok SK
Int J Mol Sci
2018[Mar]; 19
(3
): ä PMID29533969
show ga
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 ? 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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