Overexpression of nitric oxide synthases in tendon overuse.

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.

The protective effects of meniscal transplantation on cartilage. An experimental study in sheep.

BACKGROUND: Meniscal loss may result in arthritis. The aim of this study was to establish a simple operative method for meniscal transplantation in a large-animal model and to determine whether meniscal transplantation provides protection of the articular surfaces, whether meniscal allografts have the same protective effect as meniscal autogenous grafts, and whether there is any rejection phenomenon associated with meniscal allografts. METHODS: Twenty-eight sheep were divided into four study groups, which were treated with (1) a sham operation (four sheep), (2) a meniscectomy (eight sheep), (3) a meniscal autogenous graft (eight sheep), or (4) a meniscal allograft (eight sheep). The meniscal transplant was secured with three suture anchors to the tibia. At four months after the operation, macroscopic and microscopic evaluations of the articular cartilage and the menisci of the sheep knees were performed in a blinded fashion. RESULTS: The group treated with the sham operation had no cartilage damage and had normal meniscal tissue. The meniscectomies resulted in significant macroscopic and microscopic damage to the articular cartilage in the medial compartment. The mean score (and standard error of the mean) for macroscopic damage to the cartilage in the group treated with the meniscectomy was 6.5+/-0.8 points compared with 3.9+/-0.7 points in the group treated with the autogenous graft and 4.3+/-0.6 points in the group treated with the allograft (p<0.05). The size of the area of damaged articular cartilage was reduced by approximately 50 percent in both groups treated with a meniscal transplant compared with the group treated with the meniscectomy (p<0.05). There were no significant differences between the group treated with the autogenous graft and that treated with the allograft. The histological appearance of the meniscal autogenous grafts was within normal limits. Interestingly, all of the allografts had evidence of fibrinoid degeneration with areas of hypocellularity and cloning of chondroid cells. CONCLUSIONS: These results suggest that meniscal transplantation provides noticeable although not complete protection against damage to the articular cartilage after a meniscectomy. The meniscal allografts were just as effective in providing this protection as were the meniscal autogenous grafts.