Tenocyte responses to mechanical loading in vivo - A role for local insulin-like growth factor 1 signaling in early tendinosis in rats
Tenocyte responses to mechanical loading in vivo - A role for local insulin-like growth factor 1 signaling in early tendinosis in rats
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DOI：
10.1002/art.22426
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发表时间：
2007-02-01
影响因子：
--
通讯作者：
Khan, Karim M.
中科院分区：
文献类型：
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作者：
Scott, Alexander;Cook, Jill L.;Khan, Karim M.
目标。研究大鼠过度使用性冈上肌腱病发展过程中tenocyle的调控事件。以1 km/h的速度下坡，每天跑1小时，诱导冈上肌腱病变。在4周、8周、12周和16周收获肌腱，进行明场、偏振光或透射电子显微镜检查。使用改良的Bonar组织病理学量表半定量评估肌腱病的发展。细胞凋亡和细胞增殖分别用抗片段DNA抗体和增殖细胞核抗原检测。免疫组化反应计算机辅助定量测定胰岛素样生长因子1 （IGF-1）的表达。使用磷酸化胰岛素受体底物1 （IRS-1）和erk -1/2抗体探测局部IGF-1信号。在12周的下坡跑步后，出现了肌腱病，其特征是肌腱细胞变圆和增殖，以及糖胺聚糖积累和胶原断裂。CD90+细胞的增殖指数升高与肌腱病有关，并与局部IGF-1表达增加以及IRS-1和ERK-1/2磷酸化相关。各时间点均无细胞凋亡和细胞炎症。在该动物模型中，早期肌腱病变与肌腱细胞的局部刺激有关，而与外源性炎症或细胞凋亡无关。我们的数据表明，在过度使用性肌腱疾病的发病过程中，IGF-1在负荷诱导的肌腱细胞反应中发挥了作用。
Objective. To investigate tenocyle regulatory events during the development of overuse supraspinatus tendinosis in rats.Methods. Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for It 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.Results. 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.Conclusion. 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.