Lu ZuFu, Roohani-Esfahani Seyed-Iman, Li JiaoJiao, Zreiqat Hala
Biomaterials and Tissue Engineering Research Unit, School of AMME, the University of Sydney, Sydney, Australia.
Biomaterials and Tissue Engineering Research Unit, School of AMME, the University of Sydney, Sydney, Australia.
Nanomedicine. 2015 Jan;11(1):219-28. doi: 10.1016/j.nano.2014.09.008. Epub 2014 Sep 28.
The lack of complete understanding in the signalling pathways that control the osteogenic differentiation of mesenchymal stem cells hinders their clinical application in the reconstruction of large bone defects and non-union bone fractures. The aim of this study is to gain insight into the interactions of bone morphogenetic protein-2 (BMP-2) and bone biomimetic scaffolds in directing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) and the underlying signalling pathways involved. We demonstrated that bioactive glass nanoparticles (nBG) incorporated polycaprolactone (PCL) coating on hydroxyapatite/β-tricalcium phosphate (HA/TCP) scaffold exerted a synergistic effect with 3days of BMP-2 treatment in promoting osteogenic gene expression levels (Runx-2, collagen I, osteopontin and bone sialoprotein) and alkaline phosphatase activity in ASCs. Furthermore, we revealed that the synergistic effect was mediated through a mechanism of activating β1-integrin and induction of Wnt-3a autocrine signalling pathways by nBG incorporated scaffold.
对控制间充质干细胞成骨分化的信号通路缺乏全面了解,这阻碍了它们在大骨缺损修复和骨不连骨折重建中的临床应用。本研究的目的是深入了解骨形态发生蛋白-2(BMP-2)与骨仿生支架在引导脂肪组织来源的间充质干细胞(ASC)成骨分化过程中的相互作用以及相关的潜在信号通路。我们证明,在羟基磷灰石/β-磷酸三钙(HA/TCP)支架上,结合了生物活性玻璃纳米颗粒(nBG)的聚己内酯(PCL)涂层与3天的BMP-2处理在促进ASC中成骨基因表达水平(Runx-2、I型胶原、骨桥蛋白和骨唾液蛋白)和碱性磷酸酶活性方面发挥了协同作用。此外,我们发现这种协同作用是通过激活β1整合素以及由结合了nBG的支架诱导Wnt-3a自分泌信号通路的机制介导的。