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Nat Commun. 2016 Mar 24;7:10959. doi: 10.1038/ncomms10959.

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

Author information

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.

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.

PMID:
27009967
PMCID:
PMC4820810
DOI:
10.1038/ncomms10959
[Indexed for MEDLINE]
Free PMC Article

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