IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells
IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells
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DOI：
10.1016/j.bbrc.2006.05.034
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发表时间：
2006-07-07
影响因子：
3.1
通讯作者：
Brenner, Rolf E.
中科院分区：
文献类型：
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作者：
Fiedler, Joerg;Brill, Caroline;Brenner, Rolf E.
众所周知，胰岛素样生长因子 (IGF) 是骨骼生长、重塑和修复的关键调节因子。由于所有这些过程都依赖于有可能致力于成骨细胞谱系的细胞的招募，因此我们使用改良的博伊登室测定法研究了 IGF-I 和 IGF-II 对人间充质祖细胞 (MPC) 迁移的可能影响。将结果与原代成骨细胞和体外成骨分化 MPC 的结果进行比较。 IGF-I 和-II 以 1 至 100 ng/mL 的剂量依赖性方式刺激所有这些细胞群的细胞迁移。 MPC和原代成骨细胞的最大趋化指数(CI)为4-5，体外分化的MPC约为3。棋盘分析表明，IGF 刺激真正的定向细胞迁移（趋化性），而不仅仅是趋化作用。添加针对 I 型 IGF 受体（α IR3）的抗体可完全消除（MPC）或显着降低（原代成骨细胞）每种 IGF 的趋化作用。 IGFBP-3 本身没有直接作用，而 IGFBP-5 在浓度为 80 和 160 ng/mL 时刺激 MPC 迁移。并行应用 IGFBP-3 具有边缘抑制作用，而添加 40 ng/mL IGFBP-5 则增强 IGF-I 对 MPC 的趋化作用。总之，我们的结果表明IGF-I和-II是MPC的趋化因子，并表明IGFBP-5既调节IGF-I效应又直接刺激人间充质祖细胞的迁移。 (c) 2006 Elsevier Inc. 保留所有权利。
Insulin-like growth factors (IGFs) are known to be key regulators of bone growth, remodeling, and repair. Since all these processes depend on the recruitment of cells with the potential to be committed to the osteoblastic lineage, we studied possible effects of IGF-I and -II on migration of human mesenchymal progenitor cells (MPC) using a modified Boyden chamber assay. The results were compared to those of primary osteoblasts and in vitro-osteogenic-differentiated MPC. IGF-I and -II stimulated cell migration of all these cell populations in a dose-dependent manner from 1 to 100 ng/mL. The maximal chemotactic index (CI) was 4-5 for MPC and primary osteoblasts and about 3 for in vitro-differentiated MPC. Checkerboard analysis revealed that IGFs stimulated true directed cell migration (chemotaxis) and not simply chemokinesis. Addition of an antibody against the type I IGF receptor (alpha IR3) completely abolished (MPC) or markedly reduced (primary osteoblasts) the chemotactic effects of each of the IGFs. IGFBP-3 itself had no direct effect, while IGFBP-5 stimulated MPC migration at concentrations of 80 and 160 ng/mL. Parallel application of IGFBP-3 had borderline inhibitory effects while the addition of 40 ng/mL of IGFBP-5 enhanced the chemotactic effect of IGF-I on MPC. In conclusion, our results show that IGF-I and -II are chemotactic factors for MPC and indicate that IGFBP-5 both modulates the IGF-I effect and directly stimulates migration of human mesenchymal progenitor cells. (c) 2006 Elsevier Inc. All rights reserved.