Paclitaxel-mediated microtubule stabilization regulates flexor tendon repair in rats.

AIMS

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.