Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States.
Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, United States.
Elife. 2018 Nov 26;7:e38069. doi: 10.7554/eLife.38069.
Mechanical forces between cells and extracellular matrix (ECM) influence cell shape and function. Tendons are ECM-rich tissues connecting muscles with bones that bear extreme tensional force. Analysis of transgenic zebrafish expressing mCherry driven by the tendon determinant reveals that tendon fibroblasts (tenocytes) extend arrays of microtubule-rich projections at the onset of muscle contraction. In the trunk, these form a dense curtain along the myotendinous junctions at somite boundaries, perpendicular to myofibers, suggesting a role as force sensors to control ECM production and tendon strength. Paralysis or destabilization of microtubules reduces projection length and surrounding ECM, both of which are rescued by muscle stimulation. Paralysis also reduces SMAD3 phosphorylation in tenocytes and chemical inhibition of TGFβ signaling shortens tenocyte projections. These results suggest that TGFβ, released in response to force, acts on tenocytes to alter their morphology and ECM production, revealing a feedback mechanism by which tendons adapt to tension.
细胞与细胞外基质（ECM）之间的机械力影响细胞的形状和功能。肌腱是富含细胞外基质的组织，将肌肉与承受极端张力的骨骼连接起来。对表达 mCherry 的转基因斑马鱼的分析表明，在肌肉收缩开始时，肌腱成纤维细胞（tenocytes）会延伸出一系列富含微管的突起。在躯干中，这些突起在体节边界的肌-腱连接处形成密集的幕帘，与肌纤维垂直，表明其作为力传感器的作用，以控制细胞外基质的产生和肌腱的强度。微管的麻痹或不稳定会减少突起的长度和周围的细胞外基质，肌肉刺激可以挽救这两者。麻痹还会减少 tenocytes 中的 SMAD3 磷酸化，而 TGFβ 信号的化学抑制会缩短 tenocytes 突起。这些结果表明，TGFβ 在受到力的作用时释放出来，作用于 tenocytes 以改变它们的形态和细胞外基质的产生，揭示了一种反馈机制，通过该机制，肌腱适应张力。
