Author:
Yahara Yasuhito,Takemori Hiroshi,Okada Minoru,Kosai Azuma,Yamashita Akihiro,Kobayashi Tomohito,Fujita Kaori,Itoh Yumi,Nakamura Masahiro,Fuchino Hiroyuki,Kawahara Nobuo,Fukui Naoshi,Watanabe Akira,Kimura Tomoatsu,Tsumaki Noriyuki
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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Cited by
66 articles.
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