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

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.
Authors	Yasuhito Yahara, Hiroshi Takemori, Minoru Okada, Azuma Kosai, Akihiro Yamashita, Tomohito Kobayashi, Kaori Fujita, Yumi Itoh, Masahiro Nakamura, Hiroyuki Fuchino, Nobuo Kawahara, Naoshi Fukui, Akira Watanabe, Tomoatsu Kimura, Noriyuki Tsumaki
Journal	Nature communications (Nat Commun) Vol. 7 Pg. 10959 (Mar 24 2016) ISSN: 2041-1723 [Electronic] England
PMID	27009967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Indans pterosin B Protein Kinases Protein Serine-Threonine Kinases SIK3 protein, human SIK3 protein, mouse
Topics	Aged Aged, 80 and over Animals Antineoplastic Agents (pharmacology) Blotting, Western Cartilage, Articular (drug effects, metabolism, pathology) Cells, Cultured Chondrocytes (drug effects, metabolism, pathology) Female Humans Hypertrophy Immunoblotting Indans (pharmacology) Male Mice Mice, Knockout Middle Aged Organ Size Osteoarthritis, Knee (metabolism, pathology) Phosphorylation Protein Kinases (metabolism) Protein Serine-Threonine Kinases (drug effects, genetics) Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction

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