2. Academic Validation
  3. Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3

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

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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