• osteostatin improves the osteogenic activity of fibroblast growth factor-2 immobilized in si-doped hydroxyapatite in osteoblastic cells

    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1392/01/01
    • تاریخ انتشار در تی پی بین: 1392/01/01
    • تعداد بازدید: 625
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     si-doped hydroxyapatite (si-ha) is a suitable ceramic for the controlled release of agents to improve bone repair. we recently showed that parathyroid hormone-related protein (pthrp) (107–111) (osteostatin) has remarkable osteogenic features in various in vitro and in vivo systems. fibroblast growth factor (fgf)-2 modulates osteoblastic function and induces angiogenesis, and can promote osteoblast adhesion and proliferation after immobilization on si-ha. in the present study we examined whether osteostatin might improve the biological efficacy of fgf-2-coated si-ha in osteoblastic mc3t3-e1 cells in vitro. we found that si-ha/fgf-2 in the presence or absence of osteostatin (100 nm) similarly increased cell growth (by about 50%). however, addition of the latter peptide to si-ha/fgf-2 significantly enhanced gene expression of runx2, osteocalcin, vascular endothelial growth factor (vegf) and the vegf receptors 1 and 2, without significantly affecting that of fgf receptors in these cells. moreover, secreted vegf in the mc3t3-e1 cell conditioned medium, which induced the proliferation of pig endothelial-like cells, was also enhanced by these combined factors. the synergistic action of osteostatin and si-ha/fgf-2 on the vegf system was abrogated by a mitogen-activated protein kinase inhibitor (u0126) and by the calcium antagonist verapamil. this action was related to an enhancement of alkaline phosphatase activity and matrix mineralization in mc3t3-e1 cells, and also in primary human osteoblastic cells. these in vitro data show that osteostatin increases the osteogenic efficacy of a si-ha/fgf-2 biomaterial by a mechanism involving mitogen-activated protein kinases and intracellular ca2+. these findings provide an attractive strategy for bone tissue engineering.

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