Stat3 as a potential therapeutic target for rheumatoid arthritis

Takatsugu Oike, Yuiko Sato, Tami Kobayashi, Kana Miyamoto, Satoshi Nakamura, Yosuke Kaneko, Shu Kobayashi, Kengo Harato, Hideyuki Saya, Morio Matsumoto, Masaya Nakamura, Yasuo Niki, Takeshi Miyamoto

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Abstract

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.

Original languageEnglish
Article number10965
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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STAT3 Transcription Factor
Rheumatoid Arthritis
Experimental Arthritis
Joints
Arthritis
Inflammation
Therapeutics
Knockout Mice
Pharmaceutical Preparations
Chronic Disease
Tumor Necrosis Factor-alpha
Antibodies

ASJC Scopus subject areas

  • General

Cite this

Oike, T., Sato, Y., Kobayashi, T., Miyamoto, K., Nakamura, S., Kaneko, Y., ... Miyamoto, T. (2017). Stat3 as a potential therapeutic target for rheumatoid arthritis. Scientific Reports, 7(1), [10965]. https://doi.org/10.1038/s41598-017-11233-w

Stat3 as a potential therapeutic target for rheumatoid arthritis. / Oike, Takatsugu; Sato, Yuiko; Kobayashi, Tami; Miyamoto, Kana; Nakamura, Satoshi; Kaneko, Yosuke; Kobayashi, Shu; Harato, Kengo; Saya, Hideyuki; Matsumoto, Morio; Nakamura, Masaya; Niki, Yasuo; Miyamoto, Takeshi.

In: Scientific Reports, Vol. 7, No. 1, 10965, 01.12.2017.

Research output: Contribution to journalArticle

Oike T, Sato Y, Kobayashi T, Miyamoto K, Nakamura S, Kaneko Y et al. Stat3 as a potential therapeutic target for rheumatoid arthritis. Scientific Reports. 2017 Dec 1;7(1). 10965. https://doi.org/10.1038/s41598-017-11233-w
Oike, Takatsugu ; Sato, Yuiko ; Kobayashi, Tami ; Miyamoto, Kana ; Nakamura, Satoshi ; Kaneko, Yosuke ; Kobayashi, Shu ; Harato, Kengo ; Saya, Hideyuki ; Matsumoto, Morio ; Nakamura, Masaya ; Niki, Yasuo ; Miyamoto, Takeshi. / Stat3 as a potential therapeutic target for rheumatoid arthritis. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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