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Stimulation of osteogenic activity in mesenchymal stem cells by FK506
Author(s) -
Dai Wenda,
Dong Jian,
Fang Taolin,
Uemura Toshimasa
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31685
Subject(s) - osteocalcin , mesenchymal stem cell , alkaline phosphatase , ascorbic acid , osteopontin , materials science , in vivo , endocrinology , chemistry , biology , biochemistry , microbiology and biotechnology , enzyme , food science
The aim of this study was to investigate the osteogenic induction by tacrolimus hydrate (FK506) of rat bone marrow‐derived mesenchymal stem cells (MSCs). MSCs were cultured in α‐MEM containing either (1) L ‐ascorbic acid‐2‐phosphate (AsAP) and β‐glycerophosphate (β‐GP) as a control; (2) AsAP and β‐GP plus FK506; (3) AsAP and β‐GP plus Dex; or (4) AsAP and β‐GP plus FK506 and Dex. The concentration of FK506 was varied from 5 to 5000 n M to investigate the dose–effect relationship. Sixteen days later, cells were harvested for analysis. Examination of morphology, alkaline phosphatase (APase) activity, calcium deposition, bone nodule formation, osteocalcin mRNA expression, and mineralized extracellular matrix formation showed that the osteogenic differentiation of MSCs was greatly promoted, bone nodule formation was enhanced, APase activity and the expression of osteocalcin mRNA were increased. FK506 was much more effective when combined with Dex. The best results were achieved with α‐MEM containing 0.25 m M AsAP, 10 m M β‐GP, 10 n M Dex, and 50 n M FK506. Formation of bone in vivo was also studied by transplanting MSCs‐loaded ceramic cubes subcutaneously into the back of rats. Satisfactory results were achieved at 4 and 8 weeks. FK506 should be considered for use as an osteogenic agent. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008