title: 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.affiliation: 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.|Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Yahara
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemori
authors.affiliation: 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.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okada
authors.affiliation: 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.
authors.forename: Azuma
authors.initials: A
authors.lastname: Kosai
authors.affiliation: 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.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: 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.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: 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.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fujita
authors.affiliation: 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.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Genome/Epigenome Analysis Core Facility, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Research Center for Medicinal Plant Resources, Tsukuba Division, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2, Hachimandai, Tsukuba, Ibaraki 305-0843, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fuchino
authors.affiliation: Research Center for Medicinal Plant Resources, Tsukuba Division, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2, Hachimandai, Tsukuba, Ibaraki 305-0843, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kawahara
authors.affiliation: Graduate School of Arts and Sciences, Department of Life Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.affiliation: Genome/Epigenome Analysis Core Facility, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.affiliation: 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.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tsumaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006984:Hypertrophy; D015151:Immunoblotting; D007189:Indans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009929:Organ Size; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D007189:Indans; C586064:pterosin B; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C509079:SIK3 protein, human; C571369:SIK3 protein, mouse