Usman Muhammad Andry, Nakasa Tomoyuki, Shoji Takeshi, Kato Tomohiro, Kawanishi Yoshitaka, Hamanishi Michio, Kamei Naosuke, Ochi Mitsuo
Department of Orthopaedic Surgery, Integrated Health and Sciences, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan,
J Orthop Sci. 2015 May;20(3):538-46. doi: 10.1007/s00776-015-0709-5. Epub 2015 Mar 11.
Achilles tendons heal slower than other tissues, therefore requiring the developmnent of a strategy for accelerating the process. Vascular supply plays an important role in primary tendon healing, especially during the early healing phase. MicroRNA (miR)-210 has been reported as being crucial for angiogenesis, which is a key factor of tissue repair. We report herein that local injection of synthetic miR-210 into the injured Achilles tendon of a rat accelerated healing of the tendon.
Achilles tendons were transected and repaired via the Kessler suture technique in Sprague-Dawley rats. Then, double stranded (ds) miR-210 was injected into the repaired sites. The control group was injected with non-functioned dsRNA. At 2, 6 and 12 weeks, histological evaluations were performed. At two and six weeks, mechanical testing and angiogenesis were evaluated. Gene expression analysis using real-time polymerase chain reaction (PCR) and immunohistochemistry were performed at two weeks.
At two and six weeks, regular dense collagen tissue in the miR-210 group was observed and the diameter of collagen fiber in the miR-210 group was significantly higher than in the control. At two weeks, the ultimate failure load was significantly higher than in the control group, and expression of VEGF, FGF2 and type I collagen was upregulated. Abundant vessels in the miR-210 group were observed at two weeks, but there was no significant difference in vessel numbers between the two groups at six weeks. At 12 weeks, repaired Achilles tendons in the miR-210 group consisted of parallel and dense fibers, whereas wavy and loose fibers were still observed in the control group.
The current study showed that single local injection of synthetic miR-210 promotes Achilles tendon healing in the early phase.
跟腱愈合比其他组织慢，因此需要制定加速愈合过程的策略。血管供应在肌腱初期愈合中起重要作用，尤其是在愈合早期阶段。据报道，微小RNA（miR）-210对血管生成至关重要，而血管生成是组织修复的关键因素。我们在此报告，向大鼠受伤的跟腱局部注射合成的miR-210可加速肌腱愈合。
在Sprague-Dawley大鼠中，通过凯斯勒缝合技术切断并修复跟腱。然后，将双链（ds）miR-210注射到修复部位。对照组注射无功能的dsRNA。在第2、6和12周进行组织学评估。在第2周和第6周，评估力学性能测试和血管生成情况。在第2周进行实时聚合酶链反应（PCR）基因表达分析和免疫组织化学分析。
在第2周和第6周，观察到miR-210组有规则的致密胶原组织，且miR-210组胶原纤维直径明显大于对照组。在第2周，极限破坏载荷明显高于对照组，血管内皮生长因子（VEGF）、成纤维细胞生长因子2（FGF2）和I型胶原的表达上调。在第2周观察到miR-210组有丰富的血管，但在第6周两组血管数量无显著差异。在第12周，miR-210组修复的跟腱由平行且致密的纤维组成，而对照组仍观察到波浪状和松散的纤维。
目前的研究表明，单次局部注射合成的miR-210可促进跟腱早期愈合。
