Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche.
Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche.
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DOI：
10.1016/j.bpj.2021.05.021
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发表时间：
2021-07-06
影响因子：
3.4
通讯作者：
Jaspers RT
中科院分区：
文献类型：
--
作者：
Haroon M;Klein-Nulend J;Bakker AD;Jin J;Seddiqi H;Offringa C;de Wit GMJ;Le Grand F;Giordani L;Liu KJ;Knight RD;Jaspers RT
肌肉干细胞（Muscle Stem Cells，MuSC）是骨骼肌再生和体内平衡所必需的。MuSC的正常功能，包括激活、增殖和命运决定，是由MuSC与其生态位之间的一系列精心策划的事件和通信决定的。已知多种生物化学刺激物调节MuSC命运和功能。然而，除了生物化学因素之外，可以想象的是，由于MuSC和肌纤维之间的肌筋膜连接，MuSC在肌肉拉伸-缩短周期期间经受机械力。MuSC在体外对机械力做出响应，但仍有待证明物理力是否也施加在其天然生态位中的MuSC上，以及它们是否有助于MuSC的功能和命运。利用mT/mG双荧光Cre-reporter小鼠和多光子显微镜观察离体肌纤维束的机械负载导致的MuSC在其天然生态位中的变形。MuSC经受1小时的脉动流体剪切应力（PFSS），峰值剪切应力速率为6.5Pa/s。PFSS处理后，测定一氧化氮、参与调节MuSC增殖和分化、ERK 1/2、p38和AKT活化的基因的信使RNA（mRNA）表达水平。离体伸展趾长伸肌和比目鱼肌肌纤维束导致MuSC在其龛位中的压缩以及拉伸和剪切变形。MuSCs在体外对PFSS的反应是一氧化氮的产生增加和iNOS mRNA水平的上升趋势。PFSS增强了c-Fos、Cdk 4和IL-6的基因表达，而Wnt 1、MyoD、Myog、Wnt 5a、COX 2、Rspo 1、Vangl 2、Wnt 10 b和MGF的表达保持不变。PFSS处理后ERK 1/2和p38 MAPK信号也上调。我们的结论是，MuSCs在其天然生态位受到力诱导的变形，由于肌纤维拉伸缩短。此外，MuSC是机械响应性的，如通过已知促进增殖的MuSC的PFSS介导的因子表达所证明的。
Muscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche. A multitude of biochemical stimuli are known to regulate MuSC fate and function. However, in addition to biochemical factors, it is conceivable that MuSCs are subjected to mechanical forces during muscle stretch-shortening cycles because of myofascial connections between MuSCs and myofibers. MuSCs respond to mechanical forces in vitro, but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs. MuSC deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles was visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 h pulsating fluid shear stress (PFSS) with a peak shear stress rate of 6.5 Pa/s. After PFSS treatment, nitric oxide, messenger RNA (mRNA) expression levels of genes involved in regulation of MuSC proliferation and differentiation, ERK 1/2, p38, and AKT activation were determined. Ex vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to PFSS in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels. PFSS enhanced gene expression of c-Fos, Cdk4, and IL-6, whereas expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged. ERK 1/2 and p38 MAPK signaling were also upregulated after PFSS treatment. We conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive, as evidenced by PFSS-mediated expression of factors by MuSCs known to promote proliferation.
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DOI：
10.1002/jor.23797
发表时间：
2018-03
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Boers HE;Haroon M;Le Grand F;Bakker AD;Klein-Nulend J;Jaspers RT
通讯作者：
Jaspers RT
影响因子：
3.4
作者：
Delarue, Morgan;Monte, Fabien;Cappello, Giovanni
通讯作者：
Cappello, Giovanni
影响因子：
64.5
作者：
FRESHNEY, NW;RAWLINSON, L;SAKLATVALA, J
通讯作者：
SAKLATVALA, J
影响因子：
5.2
作者：
Buono, Roberta;Vantaggiato, Chiara;Pisa, Viviana;Azzoni, Emanuele;Bassi, Maria Teresa;Brunelli, Silvia;Sciorati, Clara;Clementi, Emilio
通讯作者：
Clementi, Emilio
DOI：
10.1002/jbmr.2900
发表时间：
2016-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Holguin N;Brodt MD;Silva MJ
通讯作者：
Silva MJ