Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Molecular Biology and Biochemistry, Biomedical Sciences Major, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Am J Sports Med. 2019 Jun;47(7):1701-1712. doi: 10.1177/0363546519836959. Epub 2019 Apr 30.
The effects of fibroblast growth factor 2 (FGF-2) on healing after surgical repair of chronic rotator cuff (RC) tears remain unclear.
FGF-2 enhances tenogenic healing response, leading to biomechanical and histological improvement of repaired chronic RC tears in rats.
Controlled laboratory study.
Adult male Sprague-Dawley rats (n = 117) underwent unilateral surgery to refix the supraspinatus tendon to its insertion site 3 weeks after detachment. Animals were assigned to either the FGF-2 group or a control group. The effects of FGF-2 were assessed via biomechanical tests at 3 weeks after detachment and at 6 and 12 weeks postoperatively and were assessed histologically and immunohistochemically for proliferating cell nuclear antigen and mesenchymal stem cell (MSC)-related markers at 2, 6, and 12 weeks postoperatively. The expression of tendon/enthesis-related markers, including SRY-box 9 (Sox9), scleraxis (Scx), and tenomodulin (Tnmd), were assessed by real-time reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. The effect of FGF-2 on comprehensive gene expressions at the healing site was evaluated by microarray analysis.
The FGF-2 group showed a significant increase in mechanical strength at 6 and 12 weeks compared with control; the FGF-2 group also showed significantly higher histological scores at 12 weeks than control, indicating the presence of more mature tendon-like tissue. At 12 weeks, Scx and Tnmd expression increased significantly in the FGF-2 group, whereas no significant differences in Sox9 were found between groups over time. At 2 weeks, the percentage of positive cells expressing MSC-related markers increased in the FGF-2 group. Microarray analysis at 2 weeks after surgery showed that the expression of several growth factor genes and extracellular matrix-related genes was influenced by FGF-2 treatment.
FGF-2 enhanced the formation of tough tendon-like tissues including an increase in Scx- or Tnmd-expressing cells at 12 weeks after surgical repair of chronic RC tears. The increase in mesenchymal progenitors and the changes in gene expression upon FGF-2 treatment in the early phase of healing appear to be related to a certain favorable microenvironment for tenogenic healing response of chronic RC tears.
These findings may provide advantages in therapeutic strategies for patients with RC tears.
成纤维细胞生长因子 2（FGF-2）对慢性肩袖撕裂术后愈合的影响尚不清楚。
FGF-2 增强腱形成反应，导致大鼠慢性肩袖撕裂修复后的生物力学和组织学改善。
对照实验室研究。
成年雄性 Sprague-Dawley 大鼠（n = 117）在分离后 3 周接受手术将冈上肌腱重新固定到其插入部位。动物被分配到 FGF-2 组或对照组。通过在分离后 3 周、术后 6 周和 12 周进行生物力学测试评估 FGF-2 的作用，并在术后 2、6 和 12 周进行增殖细胞核抗原和间充质干细胞（MSC）相关标志物的组织学和免疫组织化学评估。通过实时逆转录聚合酶链反应、原位杂交和免疫组织化学评估腱/腱止点相关标志物，包括性决定区 Y 框 9（Sox9）、粘连蛋白（Scx）和腱调蛋白（Tnmd）的表达。通过微阵列分析评估 FGF-2 对愈合部位综合基因表达的影响。
与对照组相比，FGF-2 组在 6 周和 12 周时机械强度显著增加；FGF-2 组在 12 周时的组织学评分也显著高于对照组，表明存在更成熟的腱样组织。在 12 周时，FGF-2 组 Scx 和 Tnmd 的表达显著增加，而 Sox9 在组间随时间无显著差异。在 2 周时，FGF-2 组表达 MSC 相关标志物的阳性细胞百分比增加。手术后 2 周的微阵列分析显示，FGF-2 处理影响了几种生长因子基因和细胞外基质相关基因的表达。
FGF-2 增强了慢性肩袖撕裂术后修复后坚韧腱样组织的形成，包括 Scx 或 Tnmd 表达细胞的增加。在愈合的早期阶段，间充质祖细胞的增加和 FGF-2 处理引起的基因表达变化似乎与慢性肩袖撕裂腱形成反应的某种有利微环境有关。
这些发现可能为肩袖撕裂患者的治疗策略提供优势。
