Cyclic Tensile Strain Can Play a Role in Directing both Intramembranous and Endochondral Ossification of Mesenchymal Stem Cells.
Cyclic Tensile Strain Can Play a Role in Directing both Intramembranous and Endochondral Ossification of Mesenchymal Stem Cells.
复制标题
DOI：
10.3389/fbioe.2017.00073
复制
发表时间：
2017
影响因子：
5.7
通讯作者：
Kelly DJ
中科院分区：
文献类型：
--
作者：
Carroll SF;Buckley CT;Kelly DJ
成功地再生受损或患病的骨和其他关节组织将需要详细了解关节特异性环境因素如何调节被招募或递送到损伤部位的祖细胞的命运。本研究的目的是探讨周期性拉伸应变（CTS）在调节间充质干细胞/多能基质细胞（MSC）分化的启动中的作用，特别是它们沿沿着软骨内途径的进展。为此，我们首先探讨了在没有任何特异性生长因子的情况下CTS对MSC分化的影响，其次，我们研究了长期应用这种机械刺激对保持在软骨形成培养条件下的MSC中的软骨内骨化标记物的影响。开发定制生物反应器以将单轴拉伸变形应用于包封在生理相关的3D纤维蛋白水凝胶内的骨髓来源的MSC。在不存在可溶性分化因子的情况下施加的机械负荷被发现增强了生腱（COL 1A 1）和成骨标志物（BMP 2、RUNX 2和ALPL）的表达，同时抑制了脂肪形成标志物。没有观察到软骨形成的证据，表明CTS可以在启动直接膜内骨化中发挥作用。在软骨形成生长因子存在下的长期培养期间，显示CTS诱导MSC重组和排列，增加蛋白聚糖和胶原蛋白的产生，并以应变量依赖性方式增强与软骨内骨化相关的标志物（BMP 2、RUNX 2、ALPL、OPN和COL 10A 1）的表达。综上所述，这些发现表明，拉伸负荷可能在促进骨髓间充质干细胞的膜内和软骨内骨化中发挥关键作用。在这两种情况下，这种负载诱导的促进成骨与成骨生长因子BMP 2的表达增加。这项研究的结果表明，外源性机械负荷在指导干细胞命运中发挥着重要作用，如果要实现其临床潜力，在设计细胞和组织工程疗法时必须仔细考虑这一点。
Successfully regenerating damaged or diseased bone and other joint tissues will require a detailed understanding of how joint specific environmental cues regulate the fate of progenitor cells that are recruited or delivered to the site of injury. The goal of this study was to explore the role of cyclic tensile strain (CTS) in regulating the initiation of mesenchymal stem cell/multipotent stromal cell (MSC) differentiation, and specifically their progression along the endochondral pathway. To this end, we first explored the influence of CTS on the differentiation of MSCs in the absence of any specific growth factor, and secondly, we examined the influence of the long-term application of this mechanical stimulus on markers of endochondral ossification in MSCs maintained in chondrogenic culture conditions. A custom bioreactor was developed to apply uniaxial tensile deformation to bone marrow-derived MSCs encapsulated within physiological relevant 3D fibrin hydrogels. Mechanical loading, applied in the absence of soluble differentiation factors, was found to enhance the expression of both tenogenic (COL1A1) and osteogenic markers (BMP2, RUNX2, and ALPL), while suppressing markers of adipogenesis. No evidence of chondrogenesis was observed, suggesting that CTS can play a role in initiating direct intramembranous ossification. During long-term culture in the presence of a chondrogenic growth factor, CTS was shown to induce MSC re-organization and alignment, increase proteoglycan and collagen production, and to enhance the expression of markers associated with endochondral ossification (BMP2, RUNX2, ALPL, OPN, and COL10A1) in a strain magnitude-dependent manner. Taken together, these findings indicate that tensile loading may play a key role in promoting both intramembranous and endochondral ossification of MSCs in a context-dependent manner. In both cases, this loading-induced promotion of osteogenesis was correlated with an increase in the expression of the osteogenic growth factor BMP2. The results of this study demonstrate the potent role that extrinsic mechanical loading plays in guiding stem cell fate, which must be carefully considered when designing cell and tissue-engineering therapies if they are to realize their clinical potential.
登录
查看更多内容
影响因子：
7.7
作者：
Holle, Andrew W.;Engler, Adam J.
通讯作者：
Engler, Adam J.
影响因子：
4.1
作者：
Baker, Brendon M.;Shah, Roshan P.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
DOI：
10.1073/pnas.1214100110
发表时间：
2013-06-18
影响因子：
11.1
作者：
Bian, Liming;Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.
影响因子：
4.9
作者：
Diederichs, Solvig;Freiberger, Friedrich;van Griensven, Martijn
通讯作者：
van Griensven, Martijn
影响因子：
2.9
作者：
Chen, Yi-Jane;Huang, Chien-Hsun;Young, Tai-Horng
通讯作者：
Young, Tai-Horng