The role of adhesion junctions in the biomechanical behaviour and osteogenic differentiation of 3D mesenchymal stem cell spheroids.
The role of adhesion junctions in the biomechanical behaviour and osteogenic differentiation of 3D mesenchymal stem cell spheroids.
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粘附连接在3D间充质干细胞球体的生物力学行为和成骨分化中的作用。
DOI：
10.1016/j.jbiomech.2017.05.014
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发表时间：
2017-07-05
影响因子：
2.4
通讯作者：
McNamara LM
中科院分区：
文献类型：
--
作者：
Griffin FE;Schiavi J;McDevitt TC;McGarry JP;McNamara LM
间充质干细胞（MSC）的成骨受机械环境的调控。与2D培养的MSCs相比，在3D球体（中间球）中培养的MSCs保留了多谱系潜力，提高了分化效率，并表现出增强的成骨基因表达和基质组成。在三维间球中，机械信号主要以细胞-细胞收缩的形式出现，由粘附连接介导，因此这种粘附连接可能在间球的成骨分化中发挥重要作用。然而，n -和ob -钙粘蛋白在中间球生物力学行为中的确切作用尚不清楚。在这里，我们使用平行板压缩对悬浮培养的中间球进行了机械测试，以评估n -钙粘蛋白和ob -钙粘蛋白粘附连接对成骨过程中中间球粘弹性特性的影响。我们的研究结果表明，n -钙粘蛋白和ob -钙粘蛋白对中间层粘弹性行为和成骨有不同的影响。当OB-cadherin沉默时，与N-cadherin沉默的中间球和用打乱siRNA （Scram）处理的中间球相比，中间球的粘度、初始和长期杨氏模量和肌动蛋白应力纤维形成在第2天增加。此外，增加的粘弹性材料特性与ob -钙粘蛋白沉默的中间球在更早的时间点（第7天）发生钙化的证据相关，而与Scram无关。有趣的是，在第14天，N-cadherin和OB-cadherin沉默的中间球都比Scram表达更高的BSP2。综上所述，这些结果表明N-cadherin和OB-cadherin都影响中间层生物力学和成骨，但作用不同。
Osteogenesis of mesenchymal stem cells (MSC) can be regulated by the mechanical environment. MSCs grown in 3D spheroids (mesenspheres) have preserved multi-lineage potential, improved differentiation efficiency, and exhibit enhanced osteogenic gene expression and matrix composition in comparison to MSCs grown in 2D culture. Within 3D mesenspheres, mechanical cues are primarily in the form of cell-cell contraction, mediated by adhesion junctions, and as such adhesion junctions are likely to play an important role in the osteogenic differentiation of mesenspheres. However the precise role of N-and OB-cadherin on the biomechanical behaviour of mesenspheres remains unknown. Here we have mechanically tested mesenspheres cultured in suspension using parallel plate compression to assess the influence of N-cadherin and OB-cadherin adhesion junctions on the viscoelastic properties of the mesenspheres during osteogenesis. Our results demonstrate that N-cadherin and OB-cadherin have different effects on mesensphere viscoelastic behaviour and osteogenesis. When OB-cadherin was silenced, the viscosity, initial and long term Young’s moduli and actin stress fibre formation of the mesenspheres increased in comparison to N-cadherin silenced mesenspheres and mesenspheres treated with a scrambled siRNA (Scram) at day 2. Additionally, the increased viscoelastic material properties correlate with evidence of calcification at an earlier time point (day 7) of OB-cadherin silenced mesenspheres but not Scram. Interestingly, both N-cadherin and OB-cadherin silenced mesenspheres had higher BSP2 expression than Scram at day 14. Taken together, these results indicate that N-cadherin and OB-cadherin both influence mesensphere biomechanics and osteogenesis, but play different roles.
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影响因子：
3
作者：
Cook, Matthew M.;Futrega, Kathryn;Doran, Michael
通讯作者：
Doran, Michael
影响因子：
2.8
作者：
Luu, Hue H.;Song, Wen-Xin;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
2.4
作者：
Darling, Eric M.;Topel, Matthew;Guilak, Farshid
通讯作者：
Guilak, Farshid
DOI：
10.1083/jcb.200405004
发表时间：
2004-09-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Engler AJ;Griffin MA;Sen S;Bönnemann CG;Sweeney HL;Discher DE
通讯作者：
Discher DE
影响因子：
14
作者：
Hsu, Shan-hui;Huang, Guo-shiang
通讯作者：
Huang, Guo-shiang