RRC ID 19173
著者 Hojo H, Yano F, Ohba S, Igawa K, Nakajima K, Komiyama Y, Kan A, Ikeda T, Yonezawa T, Woo JT, Takato T, Nakamura K, Kawaguchi H, Chung UI.
タイトル Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system.
ジャーナル J Bone Miner Metab
Abstract To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy's induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.
巻・号 28(6)
ページ 627-33
公開日 2010-11-1
DOI 10.1007/s00774-010-0179-y
PMID 20376510
MeSH Animals Antigens, Differentiation / genetics Antigens, Differentiation / metabolism Bone Morphogenetic Proteins / antagonists & inhibitors Bone Morphogenetic Proteins / genetics Bone Morphogenetic Proteins / metabolism Cell Differentiation / drug effects* Cell Line Cells, Cultured Chondrocytes / cytology Chondrocytes / drug effects* Chondrocytes / metabolism Collagen Type II / genetics Collagen Type II / metabolism Drug Evaluation, Preclinical Embryo, Mammalian Gene Expression Regulation / drug effects High-Throughput Screening Assays Inhibitor of Differentiation Protein 1 / genetics Inhibitor of Differentiation Protein 1 / metabolism Metatarsal Bones / drug effects Metatarsal Bones / metabolism Mice Mice, Inbred C57BL Osteoarthritis / drug therapy Osteogenesis / drug effects* Oxytetracycline / pharmacology* RNA, Messenger / metabolism Small Molecule Libraries Tissue Culture Techniques
IF 2.297
引用数 8
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)