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

Yasuhito Yahara, Hiroshi Takemori, Minoru Okada, Azuma Kosai, Akihiro Yamashita, Tomohito Kobayashi, Kaori Fujita, Yumi Itoh, Masahiro Nakamura, Hiroyuki Fuchino, Nobuo Kawahara, Naoshi Fukui, Akira Watanabe, Tomoatsu Kimura and Noriyuki Tsumaki ()
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Yasuhito Yahara: Center for iPS Cell Research and Application, Kyoto University
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

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10959

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