Endogenous tenocyte activation underlies the regenerative capacity of the adult zebrafish tendon.
Endogenous tenocyte activation underlies the regenerative capacity of the adult zebrafish tendon.
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DOI：
10.1038/s41536-023-00328-w
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发表时间：
2023-09-19
影响因子：
7.2
通讯作者：
Galloway, Jenna L.
中科院分区：
文献类型：
--
作者：
Tsai, Stephanie L.;Villasenor, Steffany;Shah, Rishita R.;Galloway, Jenna L.
肌腱是重要的、经常受伤的结缔组织，它将力量从肌肉传递到骨骼。它们独特的高度有序、富含基质的结构对于正常的功能至关重要。当成年哺乳动物的肌腱在急性损伤后愈合时，内源性肌腱细胞或腱细胞不能做出适当的反应，导致散乱的纤维血管瘢痕组织的形成，功能受损，再次损伤的倾向增加。在这里，我们展示了，与哺乳动物不同，成年斑马鱼腱细胞在受伤时激活并完全再生肌腱。使用成年斑马鱼颅面肌腱全撕裂损伤模型，通过多光子成像、谱系追踪和透射电子显微镜方法，确定了肌腱再生的标志阶段和细胞基础。值得注意的是，我们观察到斑马鱼肌腱在损伤后6个月(MPI)再生并恢复正常的胶原基质超微结构。肌腱再生主要经历三个阶段：损伤后24 h内的炎症反应，损伤后3~5 d断端的细胞增殖和形成细胞桥，5~6 d开始的再分化和基质重塑。重要的是，我们证明了原有的肌腱细胞是再生的主要细胞来源，在损伤时增殖和迁移，最终桥接肌腱末端。最后，我们证明转化生长因子-β信号是肌腱细胞募集和桥形成所必需的。总的来说，我们的工作首次亮相并恰当地将成年斑马鱼肌腱定位为一个无价的比较系统，以阐明可能启发新治疗策略的再生机制。
Tendons are essential, frequently injured connective tissues that transmit forces from muscle to bone. Their unique highly ordered, matrix-rich structure is critical for proper function. While adult mammalian tendons heal after acute injuries, endogenous tendon cells, or tenocytes, fail to respond appropriately, resulting in the formation of disorganized fibrovascular scar tissue with impaired function and increased propensity for re-injury. Here, we show that, unlike mammals, adult zebrafish tenocytes activate upon injury and fully regenerate the tendon. Using a full tear injury model in the adult zebrafish craniofacial tendon, we defined the hallmark stages and cellular basis of tendon regeneration through multiphoton imaging, lineage tracing, and transmission electron microscopy approaches. Remarkably, we observe that zebrafish tendons regenerate and restore normal collagen matrix ultrastructure by 6 months post-injury (mpi). Tendon regeneration progresses in three main phases: inflammation within 24 h post-injury (hpi), cellular proliferation and formation of a cellular bridge between the severed tendon ends at 3–5 days post-injury (dpi), and re-differentiation and matrix remodeling beginning from 5 dpi to 6 mpi. Importantly, we demonstrate that pre-existing tenocytes are the main cellular source of regeneration, proliferating and migrating upon injury to ultimately bridge the tendon ends. Finally, we show that TGF-β signaling is required for tenocyte recruitment and bridge formation. Collectively, our work debuts and aptly positions the adult zebrafish tendon as an invaluable comparative system to elucidate regenerative mechanisms that may inspire new therapeutic strategies.
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影响因子：
--
作者：
Diogo R;Hinits Y;Hughes SM
通讯作者：
Hughes SM
影响因子：
7.7
作者：
Kalson NS;Lu Y;Taylor SH;Starborg T;Holmes DF;Kadler KE
通讯作者：
Kadler KE
影响因子：
4.8
作者：
Koch, M;Schulze, J;Bruckner-Tuderman, L
通讯作者：
Bruckner-Tuderman, L
影响因子：
4.5
作者：
McGurk, Patrick D.;Swartz, Mary E.;Eberhart, Johann K.
通讯作者：
Eberhart, Johann K.
影响因子：
4.1
作者：
Henke，Katrin;Farmer，D'Juan T.;Youngstrom，Daniel W.
通讯作者：
Youngstrom，Daniel W.