4 years ago

Stat3 as a potential therapeutic target for rheumatoid arthritis

Morio Matsumoto, Takatsugu Oike, Yasuo Niki, Tami Kobayashi, Takeshi Miyamoto, Kengo Harato, Yosuke Kaneko, Hideyuki Saya, Kana Miyamoto, Yuiko Sato, Masaya Nakamura, Shu Kobayashi, Satoshi Nakamura
Rheumatoid arthritis (RA) is a multi-factorial disease characterized by chronic inflammation and destruction of multiple joints. To date, various biologic treatments for RA such as anti-tumor necrosis factor alpha antibodies have been developed; however, mechanisms underlying RA development remain unclear and targeted therapy for this condition has not been established. Here, we provide evidence that signal transducer and activator of transcription 3 (Stat3) promotes inflammation and joint erosion in a mouse model of arthritis. Stat3 global KO mice show early embryonic lethality; thus, we generated viable Stat3 conditional knockout adult mice and found that they were significantly resistant to collagen-induced arthritis (CIA), the most common RA model, compared with controls. We then used an in vitro culture system to screen ninety-six existing drugs to select Stat3 inhibitors and selected five candidate inhibitors. Among them, three significantly inhibited development of arthritis and joint erosion in CIA wild-type mice. These findings suggest that Stat3 inhibitors may serve as promising drugs for RA therapy.

Publisher URL: https://www.nature.com/articles/s41598-017-11233-w

DOI: 10.1038/s41598-017-11233-w

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