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

被引：72

作者：

Yahara, Yasuhito ^{[1
,2
]}

Takemori, Hiroshi ^{[3
]}

Okada, Minoru ^{[1
]}

Kosai, Azuma ^{[1
]}

Yamashita, Akihiro ^{[1
]}

Kobayashi, Tomohito ^{[1
]}

Fujita, Kaori ^{[1
]}

Itoh, Yumi ^{[3
]}

Nakamura, Masahiro ^{[4
]}

Fuchino, Hiroyuki ^{[5
]}

Kawahara, Nobuo ^{[5
]}

Fukui, Naoshi ^{[6
]}

Watanabe, Akira ^{[4
]}

Kimura, Tomoatsu ^{[2
]}

Tsumaki, Noriyuki ^{[1
]}

机构：

[1] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan

[2] Toyama Univ, Fac Med, Dept Orthopaed Surg, Sugitani, Toyama 9300194, Japan

[3] Natl Inst Biomed Innovat Hlth & Nutr, Lab Cell Signaling & Metab Dis, 7-6-8 Asagi, Saito, Ibaraki 5670085, Japan

[4] Kyoto Univ, Ctr iPS Cell Res & Applicat, Genome Epigenome Anal Core Facil, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan

[5] Natl Inst Biomed Innovat Hlth & Nutr, Res Ctr Med Plant Resources, Tsukuba Div, 1-2 Hachimandai, Tsukuba, Ibaraki 3050843, Japan

[6] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Meguro Ku, Komaba 3-8-1, Tokyo 1538902, Japan

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

ARTICULAR-CARTILAGE; ENDOCHONDRAL OSSIFICATION; COACTIVATOR TORC2; KINASE; HISTOPATHOLOGY; EXPRESSION; SURVIVAL; TISSUE;

D O I：

10.1038/ncomms10959

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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