To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF
To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF
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DOI：
10.1002/jcb.20219
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发表时间：
2004-11-15
影响因子：
4
通讯作者：
Brenner, RE
中科院分区：
文献类型：
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作者：
Fiedler, J;Etzel, N;Brenner, RE
间充质祖细胞（MPCs）的募集及其随后向成骨细胞的分化对于骨发育、重塑和修复是必需的。为了研究血小板衍生生长因子（PDGF）亚型的可能参与，检测了原代人MPC和成骨分化祖细胞（dOB）对同型二聚体人血小板衍生生长因子AA、-BB和异源二聚体PDGF-AB的趋化反应。PDGF受体的作用通过与PDGF受体α和β链特异性抗体预孵育来解决。通过加入rhPDGF-AA、rhPDGF-BB和rhPDGF-AB刺激MPC、dOB和原代成骨细胞（OB）的迁移。这种效应在MPC和rhPDGF-BB中最高，并随着成骨分化而下降。用受体α特异性抗体预孵育使CI降至临界值，而用受体β特异性抗体预处理导致对PDGF亚型的趋化反应完全丧失。在对照实验中，基础迁移值和rhBMP-2以及rxBMP-4诱导的MPC趋化性不受添加受体α或β抗体的影响。有趣的是，在没有预孵育的情况下，MPC与rhTGF-β 1的平行暴露立即导致rhPDGF-AA对迁移刺激的选择性丧失。原代人MPCs的PDGF异构体的趋化作用和成骨分化的影响表明，在骨发育和重塑过程中，MPCs的募集发挥了功能性作用。此外，这些观察可能是有用的新方法引导组织再生或骨组织工程。(C)2004 Wiley-Liss，Inc.
The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet-derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet-derived growth factor AA, -BB, and heterodimeric PDGF-AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF-AA, rhPDGF-BB, and rhPDGF-AB. The effect was highest in MPCs and for rhPDGF-BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP-2 as well as rxBMP-4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF-beta1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF-AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone. (C) 2004 Wiley-Liss, Inc.