Rolfe Rebecca A, Bastürkmen Ebru Talak, Sliney Lauren, Hayden Grace, Dunne Nicholas, Buckley Niamh, McCarthy Helen, Szczesny Spencer E, Murphy Paula
Zoology, School of Natural Sciences, Trinity College Dublin, University of Dublin, Dublin, Ireland.
School of Mechanical and Manufacturing Engineering, Dublin College University, Dublin, Ireland.
Front Cell Dev Biol. 2024 Nov 5;12:1466872. doi: 10.3389/fcell.2024.1466872. eCollection 2024.
Following early cell specification and tenocyte differentiation at the sites of future tendons, very little is known about how tendon maturation into robust load-bearing tissue is regulated. Between embryonic day (E)16 and E18 in the chick, there is a rapid change in mechanical properties which is dependent on normal embryo movement. However, the tissue, cellular and molecular changes that contribute to this transition are not well defined.
Here we profiled aspects of late tendon development (collagen fibre alignment, cell organisation and Yap pathway activity), describing changes that coincide with tissue maturation. We compared effects of rigid (constant static loading) and flaccid (no loading) immobilisation to gain insight into developmental steps influenced by mechanical cues.
We show that YAP signalling is active and responsive to movement in late tendon. Collagen fibre alignment increased over time and under static loading. Cells organise into end-to-end stacked columns with increased distance between adjacent columns, where collagen fibres are deposited; this organisation was lost following both types of immobilisation.
We conclude that specific aspects of tendon maturation require controlled levels of dynamic muscle-generated stimulation. Such a developmental approach to understanding how tendons are constructed will inform future work to engineer improved tensile load-bearing tissues.
在未来肌腱部位的早期细胞特化和肌腱细胞分化之后，关于肌腱如何成熟为强健的承重组织的调控机制，我们了解甚少。在鸡胚胎发育的第16天（E16）至第18天（E18）之间，其力学性能会发生快速变化，这依赖于胚胎的正常运动。然而，促成这种转变的组织、细胞和分子变化尚未明确界定。
在此，我们剖析了肌腱发育后期的各个方面（胶原纤维排列、细胞组织和Yap信号通路活性），描述了与组织成熟同时发生的变化。我们比较了刚性（恒定静态加载）和松弛（无加载）固定的影响，以深入了解受机械信号影响的发育步骤。
我们发现YAP信号在肌腱发育后期具有活性且对运动有反应。随着时间推移以及在静态加载下，胶原纤维排列增加。细胞组织成端对端堆叠的柱状结构，相邻柱之间的距离增加，胶原纤维沉积于此；两种类型的固定处理后，这种组织结构均消失。
我们得出结论，肌腱成熟的特定方面需要动态肌肉产生的刺激达到可控水平。这种理解肌腱构建方式的发育学方法将为未来设计改良的抗拉承重组织的工作提供参考。
