Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
ACS Nano. 2013 Aug 27;7(8):6928-38. doi: 10.1021/nn402118s. Epub 2013 Aug 5.
Nanotopographic cues from biomaterials exert powerful effects on the osteogenic differentiation of mesenchymal stem cells because of their niche-mimicking features. However, the biological mechanisms underlying cell lineage determination by surface nanotopography have not been clearly elucidated. Here, we explored the osteogenic behavior of human bone marrow mesenchymal stem cells (hBMSCs) on poly-l-lactide nanofibers with different orientations and monitored the dynamic changes in global gene expression triggered by topographical cues. RT-PCR analysis of osteogenic marker genes and ALP activity assays demonstrated that hBMSCs cultured on random nanofibers showed enhanced osteogenic-specific fate compared with those on aligned nanofibers. Microarray analysis demonstrated a similar temporal change in gene expression patterns between hBMSCs cultured on random nanofibers and those induced with an osteogenic supplement (OS). However, the extent of osteogenic differentiation on the fibrous scaffold was much lower than that driven by chemical OS. In-depth pathway analysis revealed that focal adhesion kinase, TGF-β, Wnt, and MAPK pathways were involved in the activation of osteogenic differentiation in hBMSCs on random nanofibers. These findings suggested that a lower extent but similar rhythm of dynamic cellular behavior was induced on random nanofibers when compared with the OS condition and that mechanotransduction could trigger nonspecific and multilevel responses in hBMSCs. This study provides insight into the regulation of osteogenesis directed by substratum surfaces.
生物材料的纳米形貌特征模拟了细胞微环境，对间充质干细胞的成骨分化具有显著影响。然而，表面纳米形貌影响细胞谱系分化的生物学机制仍不清楚。本研究探索了不同取向的聚 L-乳酸纳米纤维对人骨髓间充质干细胞（hBMSCs）成骨行为的影响，并监测了由形貌特征引发的细胞整体基因表达的动态变化。成骨标志物基因的 RT-PCR 分析和 ALP 活性测定表明，与定向纳米纤维相比，培养在随机纳米纤维上的 hBMSCs 表现出增强的成骨特异性命运。微阵列分析表明，培养在随机纳米纤维上的 hBMSCs 和用成骨补充剂（OS）诱导的 hBMSCs 的基因表达模式具有相似的时间变化。然而，纤维支架上的成骨分化程度远低于化学 OS 驱动的程度。深入的通路分析表明，粘着斑激酶、TGF-β、Wnt 和 MAPK 通路参与了随机纳米纤维上 hBMSCs 成骨分化的激活。这些发现表明，与 OS 条件相比，随机纳米纤维诱导的细胞行为虽然程度较低，但节奏相似，机械转导可以在 hBMSCs 中引发非特异性和多层次的反应。本研究为研究基底表面指导的成骨作用的调控提供了思路。
