Scott Alexander, Cook Jill L, Hart David A, Walker David C, Duronio Vincent, Khan Karim M
University of British Columbia, Vancouver, British Columbia, Canada.
Arthritis Rheum. 2007 Mar;56(3):871-81. doi: 10.1002/art.22426.
To investigate tenocyte regulatory events during the development of overuse supraspinatus tendinosis in rats.
Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for 1 hour a day. Tendons were harvested at 4, 8, 12, and 16 weeks and processed for brightfield, polarized light, or transmission electron microscopy. The development of tendinosis was assessed semiquantitatively using a modified Bonar histopathologic scale. Apoptosis and proliferation were examined using antibodies against fragmented DNA or proliferating cell nuclear antigen, respectively. Insulin-like growth factor 1 (IGF-1) expression was determined by computer-assisted quantification of immunohistochemical reaction. Local IGF-1 signaling was probed using antibodies to phosphorylated insulin receptor substrate 1 (IRS-1) and ERK-1/2.
Tendinosis was present after 12 weeks of downhill running and was characterized by tenocyte rounding and proliferation as well as by glycosaminoglycan accumulation and collagen fragmentation. The proliferation index was elevated in CD90+ tenocytes in association with tendinosis and correlated with increased local IGF-1 expression by tenocytes and phosphorylation of IRS-1 and ERK-1/2. Both apoptosis and cellular inflammation were absent at all time points.
In this animal model, early tendinosis was associated with local stimulation of tenocytes rather than with extrinsic inflammation or apoptosis. Our data suggest a role for IGF-1 in the load-induced tenocyte responses during the pathogenesis of overuse tendon disorders.
研究大鼠过度使用性冈上肌腱病发展过程中肌腱细胞的调节事件。
通过让大鼠以1公里/小时的速度下坡跑每天1小时来诱导冈上肌腱病。在4、8、12和16周时采集肌腱，进行明场、偏振光或透射电子显微镜检查。使用改良的博纳尔组织病理学量表对肌腱病的发展进行半定量评估。分别使用针对DNA片段化或增殖细胞核抗原的抗体检测细胞凋亡和增殖情况。通过计算机辅助定量免疫组化反应来测定胰岛素样生长因子1（IGF-Ⅰ）的表达。使用针对磷酸化胰岛素受体底物1（IRS-1）和ERK-1/2的抗体来探测局部IGF-1信号传导。
下坡跑12周后出现肌腱病，其特征为肌腱细胞变圆、增殖以及糖胺聚糖积累和胶原片段化。与肌腱病相关的CD90+肌腱细胞增殖指数升高，且与肌腱细胞局部IGF-1表达增加以及IRS-1和ERK-1/2磷酸化相关。在所有时间点均未出现细胞凋亡和细胞炎症。
在该动物模型中，早期肌腱病与肌腱细胞的局部刺激有关，而非与外部炎症或细胞凋亡有关。我们的数据表明IGF-1在过度使用性肌腱疾病发病机制中负荷诱导的肌腱细胞反应中发挥作用。
