Szomor Z L, Appleyard R C, Murrell G A C
Orthopaedic Research Institute, St. George Hospital Campus, University of New South Wales, 4-10 South Street, Kogarah, Sydney, NSW 2217, Australia.
J Orthop Res. 2006 Jan;24(1):80-6. doi: 10.1002/jor.20009.
Tendon disorders with a chronic nature, including the rotator cuff, are extremely common, and represent a major clinical problem. Mechanical overload has been proposed as an important etiologic factor in tendinopathies. Nitric oxide (NO), a free radical produced by nitric oxide synthases (NOSs), is a potent regulator and stimulator of biological processes including tendon degeneration and healing. It is also involved in response to mechanical stimuli in different tissues. In an animal model of acutely injured tendon healing temporal and differential expression of NOS isoforms has been demonstrated, suggesting that different patterns of NOSs expression may have different biological functions. Therefore, we hypothesized that tendon overuse may result in a differential upregulation of NOSs, particularly iNOS. An animal model of supraspinatus tendon overuse was utilized, which consisted of treadmill running. A group of animals of the same strain and age subjected to normal cage activity were used as controls. Following a 4-week exercise protocol supraspinatus tendons were harvested, RNA was extracted, and subjected to competitive reverse transcription and polymerase chain reaction (RT-PCR) to determine the expression levels of inducible-, endothelial-, and neuronal-NOS isoforms (i-, e-, and nNOS). The mRNA expression of all three NOS isoforms increased in the supraspinatus tendons as a result of overuse exercise. iNOS and eNOS mRNA expression increased fourfold (p < 0.01), and there was an increase, but statistically not significant, in nNOS mRNA expression in the overused tendons when compared with the controls. This study is the first to show that NOS isoforms are upregulated in rotator cuff tendon as a result of chronic overuse, and suggests the involvement of nitric oxide in the response of tendon tissue to increased mechanical stress.
包括肩袖肌腱在内的慢性肌腱疾病极为常见，是一个重大的临床问题。机械过载被认为是肌腱病的一个重要病因。一氧化氮（NO）是由一氧化氮合酶（NOS）产生的一种自由基，是包括肌腱退变和愈合在内的生物过程的有力调节者和刺激者。它还参与不同组织对机械刺激的反应。在急性损伤肌腱愈合的动物模型中，已证实NOS亚型存在时间和差异表达，这表明不同的NOS表达模式可能具有不同的生物学功能。因此，我们推测肌腱过度使用可能导致NOS，特别是诱导型NOS（iNOS）的差异性上调。我们利用了一个冈上肌腱过度使用的动物模型，该模型包括跑步机跑步。将一组相同品系和年龄、进行正常笼内活动的动物作为对照。在进行为期4周的运动方案后，采集冈上肌腱，提取RNA，并进行竞争性逆转录和聚合酶链反应（RT-PCR），以确定诱导型、内皮型和神经型NOS亚型（iNOS、eNOS和nNOS）的表达水平。由于过度使用运动，冈上肌腱中所有三种NOS亚型的mRNA表达均增加。iNOS和eNOS的mRNA表达增加了四倍（p < 0.01），与对照组相比，过度使用的肌腱中nNOS的mRNA表达有所增加，但在统计学上不显著。本研究首次表明，由于慢性过度使用，肩袖肌腱中的NOS亚型上调，提示一氧化氮参与了肌腱组织对机械应力增加的反应。
