Depletion of Scleraxis-lineage cells during tendon healing transiently impairs multi-scale restoration of tendon structure during early healing.
Depletion of Scleraxis-lineage cells during tendon healing transiently impairs multi-scale restoration of tendon structure during early healing.
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DOI：
10.1371/journal.pone.0274227
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肌腱是由异质细胞环境组成的，以硬化系（ScxLin）细胞为主。尽管ScxLin细胞是维持肌腱稳态所必需的，但它们在肌腱愈合过程中的功能尚不清楚。为此，我们首先表征了肌腱愈合过程中ScxLin细胞的时空动态，并发现整个ScxLin细胞池不断扩大，直至早期重塑愈合阶段。为了更好地确定ScxLin细胞在愈合后期增殖阶段的功能，我们在术后14-18天使用Scx-Cre诱导耗尽ScxLin细胞；Rosa-DTR小鼠模型，局部给予白喉毒素诱导愈合肌腱中ScxLin细胞凋亡。在术后第28天，与WT相比，ScxLin细胞缺失的肌腱（DTRScxLin）在结构和功能上都有很大的损伤，这表明ScxLin细胞在肌腱愈合中的重要性。接下来，利用bulk RNAseq来确定ScxLin缺失受损的潜在机制，并揭示ScxLin缺失诱导D28愈合过程的分子和形态停滞。然而，这种停滞是短暂的，因此DTRScxLin中的D56肌腱力学与野生型修复没有显著差异。总的来说，这些数据为肌腱愈合过程中ScxLin细胞的动力学和作用提供了基础知识。
Tendons are composed of a heterogeneous cell environment, with Scleraxis-lineage (ScxLin) cells being the predominant population. Although ScxLin cells are required for maintenance of tendon homeostasis, their functions during tendon healing are unknown. To this end, we first characterized the spatiotemporal dynamics of ScxLin cells during tendon healing, and identified that the overall ScxLin pool continuously expands up to early remodeling healing phase. To better define the function of ScxLin cells during the late proliferative phase of healing, we inducibly depleted ScxLin cells from day 14–18 post-surgery using the Scx-Cre; Rosa-DTR mouse model, with local administration of diphtheria toxin inducing apoptosis of ScxLin cells in the healing tendon. At D28 post-surgery, ScxLin cell depleted tendons (DTRScxLin) had substantial impairments in structure and function, relative to WT, demonstrating the importance of ScxLin cells during tendon healing. Next, bulk RNAseq was utilized to identify the underlying mechanisms that were impaired with depletion and revealed that ScxLin depletion induced molecular and morphological stagnation of the healing process at D28. However, this stagnation was transient, such that by D56 tendon mechanics in DTRScxLin were not significantly different than wildtype repairs. Collectively, these data offer fundamental knowledge on the dynamics and roles of ScxLin cells during tendon healing.
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影响因子：
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作者：
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DOI：
10.1016/j.jmbbm.2015.08.022
发表时间：
2016-01
影响因子：
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通讯作者：
Buckley MR