Journal Article Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

Yahara, Yasuhito  ,  Takemori, Hiroshi  ,  Okada, Minoru  ,  Kosai, Azuma  ,  Yamashita, Akihiro  ,  Kobayashi, Tomohito  ,  Fujita, Kaori  ,  Itoh, Yumi  ,  Nakamura, Masahiro  ,  Fuchino, Hiroyuki  ,  Kawahara, Nobuo  ,  Fukui, Naoshi  ,  Watanabe, Akira  ,  Kimura, Tomoatsu  ,  Tsumaki, Noriyuki

72016-03-24 , Nature Publishing Group
植物由来成分であるプテロシンBはSIK3を阻害し変形性関節症の治療薬開発のリード化合物となる. 京都大学プレスリリース. 2016-03-31.
Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic.

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