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

  • Nat Commun. 2016 Mar 24;7:10959. doi: 10.1038/ncomms10959.
Yasuhito Yahara  1  2 ,  Hiroshi Takemori  3 ,  Minoru Okada  1 ,  Azuma Kosai  1 ,  Akihiro Yamashita  1 ,  Tomohito Kobayashi  1 ,  Kaori Fujita  1 ,  Yumi Itoh  3 ,  Masahiro Nakamura  4 ,  Hiroyuki Fuchino  5 ,  Nobuo Kawahara  5 ,  Naoshi Fukui  6 ,  Akira Watanabe  4 ,  Tomoatsu Kimura  2 ,  Noriyuki Tsumaki  1
Affiliations
  • 1. Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
  • 2. Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
  • 3. Laboratory of Cell Signaling and Metabolic Disease, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Asagi, Saito, Ibaraki, Osaka 567-0085, Japan.
  • 4. Genome/Epigenome Analysis Core Facility, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
  • 5. Research Center for Medicinal Plant Resources, Tsukuba Division, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2, Hachimandai, Tsukuba, Ibaraki 305-0843, Japan.
  • 6. Graduate School of Arts and Sciences, Department of Life Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan.
PMID: 27009967 DOI: 10.1038/ncomms10959
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.

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