Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system
Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system
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DOI：
10.1007/s00774-010-0179-y
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Chung, Ung-il
中科院分区：
文献类型：
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作者：
Hojo, Hironori;Yano, Fumiko;Chung, Ung-il
为了有效地治疗退行性关节疾病，包括骨关节炎（OA），需要开发小的化学化合物，可以有效地诱导软骨分化，而不促进终末分化。为此，我们使用Co 12 GFP-ATDC 5系统筛选天然和合成化合物文库，并将土霉素（Oxy）鉴定为软骨形成化合物。氧诱导ATDC 5细胞中软骨基质合成和软骨细胞标志物的mRNA表达。此外，氧抑制矿化和终末软骨细胞分化标志物在ATDC 5细胞，原代软骨细胞，和培养的跖骨的mRNA表达。氧的诱导Co 12 mRNA的表达减少了添加头蛋白，并增加了添加BMP 2。此外，Oxy增加Idl、Bmp 2、Bmp 4和Bmp 6的mRNA表达。这些数据表明，氧诱导软骨分化的BMP依赖性的方式，并抑制终端分化。氧可用于治疗OA，也可用于软骨组织的再生。
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 Co12GFP-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 Co12 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Idl, 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.