Yang Juan Juan, Xu Si Wei, Zhang Xu You, Mao Wei Feng, Wu Ya Fang
Hand Surgery Research Center & Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Department of Anatomy, Medical School, Nantong, China.
Bone Joint Res. 2025 Aug 6;14(8):685-695. doi: 10.1302/2046-3758.148.BJR-2024-0484.R1.
Tendon healing is a considerable challenge in hand surgery, and the outcome depends on the function of tenocytes and homeostasis of the extracellular matrix. Although microtubule dynamics play crucial roles in various cellular processes, their function in tenocytes remains unknown. This study aimed to investigate the effects of microtubule-targeting agents (paclitaxel and vincristine) on tenocytes, focusing on their influence on tenocyte proliferation and extracellular matrix synthesis. The regulatory effects of microtubule polymerization on tendon healing were also evaluated in vivo.
A total of 200 four-week-old female C57BL/6 mice were euthanized. Tenocytes were isolated from the flexor digitorum profundus tendons of the index, middle, and ring fingers of the hind paws. The tendon cells were exposed to various concentrations (0, 10, 25, 50, 100, and 200 nM) of paclitaxel or vincristine for 24, 48, 72, and 96 hours, respectively. A rat tendon injury model was established by transecting and repairing the flexor digitorum longus (FDL) tendon, and a paclitaxel-loaded GleMA hydrogel delivery system was applied locally.
We found that both paclitaxel-induced microtubule polymerization and vincristine-induced depolymerization increased the viability of tenocytes. However, only paclitaxel treatment facilitated cell proliferation and stimulated the reorganization of microtubules. Additionally, the expression of cyclin-dependent kinase 1 (CDK1), type III collagen (Col III), and matrix metalloproteinase-3 (MMP-3) was significantly higher when the cells were treated with paclitaxel rather than vincristine treatment. In vivo analysis study using a hydrogel-paclitaxel delivery system revealed significantly improved digit flexion function, increased expression of Col III and MMP-3, and enhanced tissue repair in a rat FDL tendon injury model.
Paclitaxel-mediated microtubule polymerization promotes tenocyte proliferation and extracellular matrix synthesis, ultimately improving tendon healing in a rat model of flexor tendon injury. These improvements were associated with elevated expression of Col III and MMP-3 in tenocytes.
肌腱愈合是手外科面临的一项重大挑战，其结果取决于肌腱细胞的功能和细胞外基质的稳态。尽管微管动力学在各种细胞过程中发挥着关键作用，但其在肌腱细胞中的功能仍不清楚。本研究旨在探讨微管靶向药物（紫杉醇和长春新碱）对肌腱细胞的影响，重点关注其对肌腱细胞增殖和细胞外基质合成的影响。还在体内评估了微管聚合对肌腱愈合的调节作用。
共对200只四周龄雌性C57BL/6小鼠实施安乐死。从后爪示指、中指和环指的指深屈肌腱中分离出肌腱细胞。将肌腱细胞分别暴露于不同浓度（0、10、25、50、100和200 nM）的紫杉醇或长春新碱中24、48、72和96小时。通过横断和修复趾长屈肌（FDL）肌腱建立大鼠肌腱损伤模型，并局部应用负载紫杉醇的GleMA水凝胶递送系统。
我们发现，紫杉醇诱导的微管聚合和长春新碱诱导的解聚均增加了肌腱细胞的活力。然而，只有紫杉醇处理促进了细胞增殖并刺激了微管的重组。此外，与长春新碱处理相比，用紫杉醇处理细胞时，细胞周期蛋白依赖性激酶1（CDK1）、III型胶原（Col III）和基质金属蛋白酶-3（MMP-3）的表达显著更高。使用水凝胶-紫杉醇递送系统的体内分析研究显示，在大鼠FDL肌腱损伤模型中，趾屈曲功能显著改善，Col III和MMP-3的表达增加，组织修复增强。
紫杉醇介导的微管聚合促进肌腱细胞增殖和细胞外基质合成，最终改善屈肌腱损伤大鼠模型中的肌腱愈合。这些改善与肌腱细胞中Col III和MMP-3表达的升高有关。
