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

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  • Yasuhito Yahara

    (Center for iPS Cell Research and Application, Kyoto University
    Faculty of Medicine, University of Toyama)

  • Hiroshi Takemori

    (Laboratory of Cell Signaling and Metabolic Disease, National Institutes of Biomedical Innovation, Health and Nutrition)

  • Minoru Okada

    (Center for iPS Cell Research and Application, Kyoto University)

  • Azuma Kosai

    (Center for iPS Cell Research and Application, Kyoto University)

  • Akihiro Yamashita

    (Center for iPS Cell Research and Application, Kyoto University)

  • Tomohito Kobayashi

    (Center for iPS Cell Research and Application, Kyoto University)

  • Kaori Fujita

    (Center for iPS Cell Research and Application, Kyoto University)

  • Yumi Itoh

    (Laboratory of Cell Signaling and Metabolic Disease, National Institutes of Biomedical Innovation, Health and Nutrition)

  • Masahiro Nakamura

    (Genome/Epigenome Analysis Core Facility, Center for iPS Cell Research and Application, Kyoto University)

  • Hiroyuki Fuchino

    (Research Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition)

  • Nobuo Kawahara

    (Research Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition)

  • Naoshi Fukui

    (Graduate School of Arts and Sciences, The University of Tokyo)

  • Akira Watanabe

    (Genome/Epigenome Analysis Core Facility, Center for iPS Cell Research and Application, Kyoto University)

  • Tomoatsu Kimura

    (Faculty of Medicine, University of Toyama)

  • Noriyuki Tsumaki

    (Center for iPS Cell Research and Application, Kyoto University)

Abstract

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.

Suggested Citation

  • Yasuhito Yahara & Hiroshi Takemori & Minoru Okada & Azuma Kosai & Akihiro Yamashita & Tomohito Kobayashi & Kaori Fujita & Yumi Itoh & Masahiro Nakamura & Hiroyuki Fuchino & Nobuo Kawahara & Naoshi Fuk, 2016. "Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10959
    DOI: 10.1038/ncomms10959
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