FK506 induces chondrogenic differentiation of clonal mouse embryonic carcinoma cells, ATDC5.
FK506 (Tacrolimus) and cyclosporin A exert their immunosuppressive effects via a common mechanism, calcineurin inhibition, after binding to intracellular proteins termed immunophilins: FK506-binding protein (FKBP) and cyclophilin. In this study, FK506 was found to induce chondrogenic differentiation of ATDC5 cells (clonal mouse embryonal carcinoma cells) in a concentration-dependent manner (0.1-1000 ng/ml). Immunohistochemical staining showed that ATDC5 cells induced to differentiate by FK506 produced proteoglycan and type II collagen, main components of the extracellular matrix of cartilage. Rapamycin, an immunosuppressant that binds to FKBP, antagonized the effect of FK506. Cyclosporin A did not induce chondrogenesis at concentrations up to 1000 ng/ml. Taken together, these results suggest that FK506 induces chondrogenic differentiation of ATDC5 cells via a calcineurin-independent mechanism, after binding to FKBP.
Nishigaki
Fusako
F
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 2-1-6, Kashima, Yodogawa, Osaka 532-8514, Japan. fusako_nishigaki@po.fujisawa.co.jp
Sakuma
Shozo
S
Ogawa
Toshikazu
T
Miyata
Susumu
S
Ohkubo
Toshitaka
T
Goto
Toshio
T
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus