Adeno-associated virus-2-mediated TGF-β1 microRNA transfection inhibits adhesion formation after digital flexor tendon injury

Abstract

Adhesion formation after digital flexor tendon injury greatly affects gliding function of the tendon, which is a major clinical complication after hand surgery. Transforming growth factor beta 1 (TGF-β1) has a critical role in adhesion formation during tendon healing. Persistent regulation of TGF-β1 through application of microRNA (miRNA) specifically inhibiting the function of TGF-β1 (TGF-β1-miRNA) holds promise for treatment of such a complication. Adeno-associated virus (AAV) was used to transfer TGF-β1-miRNA to the chicken digital flexor tendons, which had been injured and surgically repaired. Four doses of AAV2-TGF-β1-miRNA (2 × 1011, 2 × 1010, 2 × 109 and 2 × 108 vector genomes (vg)) were used to determine the transfection efficiency. At postoperative 3 weeks, we found a positive correlation between the administered AAV2-TGF-β1-miRNA doses and transfection efficiency. The transfection rate ranged from 10% to 77% as the doses increased. Production of TGF-β1 protein in the tendons decreased on increasing vector dosage. When 2 × 1011 and 2 × 1010 vg were injected into the tendon, gliding excursion of the repaired tendon and work of flexion of chicken toes were significantly increased and adhesion score decreased 6 and 8 weeks later, indicating the improvement of tendon gliding and decreases in adhesion formations. However, the ultimate strength of the tendons transfected at the dose of 2 × 1010 vg was 12–24% lower than that of the control tendons. The results of this study demonstrate that application of TGF-β1-miRNA had a mixed impact on tendon healing: adhesion around the tendon is reduced but strength of the tendon healing is adversely affected. Future studies should aim at maintaining the beneficial effects of reducing tendon adhesions, while eliminating the adverse effects of decreasing the healing strength.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (Nos. 81271985, 81030035), the Priority of Academic Program Development of Jiangsu Higher Education Institutions.

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Correspondence to J B Tang.

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Wu, Y., Mao, W., Zhou, Y. et al. Adeno-associated virus-2-mediated TGF-β1 microRNA transfection inhibits adhesion formation after digital flexor tendon injury. Gene Ther 23, 167–175 (2016). https://doi.org/10.1038/gt.2015.97

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