Rat supraspinatus tendon expresses cartilage markers with overuse.

The goals of this study were to investigate the response of the rat supraspinatus tendon to overuse at the molecular level using transcriptional profiling, and to identify potential markers of tendinopathy. Adult rats were subjected to an overuse protocol that consists of downhill running (10% grade) at 17 m/min for 1 h/day, 5 days/week, for a total of either 1, 2, or 4 weeks. Another group of rats served as nonrunning time 0 controls. Transcriptional profiling was performed on the supraspinatus and patellar tendons using an Affymetrix rat genome array. A gene was considered to be differentially expressed if the p value from an ANOVA test was less than 0.01 and the difference between runners and controls was at least twofold at any time point. The supraspinatus tendon had increased expression of well-known cartilage genes such as col2a1, aggrecan, and sox9. These genes were not regulated in the patellar tendon, an internal comparator. Few genes associated with inflammation, or angiogenesis, were differentially expressed, and no significant change in the regulation of matrix metalloproteinases was detected. The results of this study suggest that by expressing more cartilage genes, the tendon is converting toward a fibrocartilage phenotype as a result of the repetitive loading and repeated compression of the tendon as it passes through the acromial arch.

IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.

Overuse injuries and trauma in tendon often involve acute or chronic pain and eventual matrix destruction. Anti-inflammatory drugs have been used as a treatment, however, the cellular and molecular mechanisms of the destructive processes in tendon are not clearly understood. It is thought that an inflammatory event may be involved as an initiating factor. Mediators of the inflammatory response include cytokines released from macrophages and monocytes. Interleukin-1 beta (IL-1 beta) is a candidate proinflammatory cytokine that is active in connective tissues such as bone and cartilage. We hypothesized that tendon cells would express receptors and respond to IL-1 beta in an initial "molecular inflammation" cascade, that is, connective tissue cell expression of cytokines that induce matrix destructive enzymes. This cascade results in expression of matrix metalloproteinases (MMPs) and aggrecanases that may lead to matrix destruction. Normal human tendon cells from six patients were isolated, grown to quiescence and treated with human recombinant IL-1 beta in serum-free medium for 16 h. Total RNA was isolated and mRNA expression assessed by semiquantitative RT-PCR. IL-1 beta (1 nM) induced mRNAs for cyclooxygenase 2 (COX2), MMP-1, -3, -13 and aggrecanase-1 as well as IL-1 beta and IL-6, whereas mRNAs for COX1 and MMP-2 were expressed constitutively. The IL-1 beta-treated tendon cells released prostaglandin E(2) (PGE(2)) in the medium, suggesting that the inducible COX2 catalyzed this synthesis. Induction of PGE(2) was detectable at 10 pM IL-1 beta. IL-1 beta also stimulated MMP-1 and -3 protein secretion. Induction of MMP-1 and -3 was detectable at 10 pM IL-1 beta. Post-injury or after some other inciting events, exogenous IL-1 beta released upon bleeding or as leakage of local capillaries may drive a proinflammatory response at the connective tissue cell level. The resulting induction of COX2, MMP-1 and -3 may underscore a potential for nonlymphocyte-mediated cytokine production of MMPs that causes matrix destruction and a loss of tendon biomechanical properties. Endogenous IL-1 beta might contribute to the process through a positive feedback loop by stimulating expression and accumulation of MMPs in the tendon matrix.

Response of rabbit Achilles tendon to chronic repetitive loading.

The objective of this work was to assess the response of tendon to chronic repetitive loading. Controlled muscle stimulation was used to load the rabbit Achilles tendon at a frequency of 1.25 Hz for two hours per day, three days per week for a period of 11 weeks. Average peak tendon force was 26 N during the protocol. The loading protocol did not modify the gross morphology of the tissue, nor its water content or cellularity. Increases in mRNA expression of collagen Type III and MMPs were observed, but no signs of injury were detected by histologic examination of tendon and paratenon structures. The lack of a detectable injury response suggests that the tendons were not loaded beyond their capacity for repair. Factors additional to mechanical loading such as aging, illness or stress may be necessary to produce pathology.

Can sonography predict the outcome in patients with achillodynia?

PURPOSE: We evaluated whether the grade assigned to the Achilles tendon's appearance on sonograms can be used to predict the outcome of achillodynia. METHODS: A retrospective evaluation was done of a case series of patients with Achilles tendon pain seen at a sports medicine clinic. The study consisted of chart reviews, telephone follow-up interviews, and grading of ultrasound images of the tendon obtained during the initial visit. The grading scheme was as follows: grade 1, normal tendon; grade 2, enlarged tendon; and grade 3, tendon containing a hypoechoic area, regardless of size. The time needed to recover from symptoms was compared between grades using survival analysis. RESULTS: The group consisted of 33 patients, with a mean age of 35.8 years and a mean follow-up time of 24.3 months. There was a statistically significant difference in the time to full recovery between grades (p = 0.02). Patients with grade 1 tendons had a prompter resolution of symptoms than did patients with grade 2 or 3 tendons. CONCLUSIONS: This retrospective study of the outcome of achillodynia demonstrates the possible use of tendon sonography as a prognostic tool to supplement physical examination.

Gender and neurogenic variables in tendon biology and repetitive motion disorders.

The incidence of repetitive motion disorders is increasing. Numerous studies have indicated that the incidence in females exceeds that in males. Some of the evidence regarding gender related factors in tendon biology is discussed and new data related to the regulation of gene expression in an animal model of tendon overuse, the determination of sex hormone receptors in tendons, and the influence of pregnancy associated factors on gene expression in four different tendons is provided. Furthermore, because neurogenic mechanisms may contribute to inflammatory conditions, new evidence is provided that supports the concept that neurotransmitters can influence expression of genes that could participate in such inflammation. By increasing our understanding of the regulation of tendon cellular and molecular biology, new approaches to preventing disease development and treatment of existing disease may evolve.

Evaluation of the implantable force transducer for chronic tendon-force recordings.

In vivo force measurements from tendons and ligaments have become an important technique to determine internal forces, joint loading, and mechanisms of neuromotor control. The most frequently used transducers for such force recordings were placed external to the target tissue. Because of space restrictions and the associated impingement artifacts, these external transducers cannot be used for force measurements in all tendons and ligaments. In these situations, transducers placed inside the target tissue have been used recently; however, the suitability and performance characteristics of these internal transducers have not been assessed systematically. The purpose of this study was to assess the suitability and performance characteristics of an internally placed force transducer which has been used previously. The results indicated that small angular displacements of the transducer within the target tissue, as well as small relative rotations of the corresponding bones, resulted in substantially changed transducer output for given externally applied loads. Also, the transducer output was found to depend on the rate of load application. It was concluded that, although the internal force transducer gave reliable signals within a given experiment, and thus, could be used to assess relative changes in tissue forces pre- and post-interventions, it would be difficult to use the transducer for the accurate determination of the actual tissue forces during unrestrained animal locomotion.

Exercise loading of tendons and the development of overuse injuries. A review of current literature.

This review examines recent studies on the effects of exercise on tendons in animal models. Although tendon adaptation to exercise has been described using histology, morphometry, ultrasonography and molecular biology, precise measurements of excess tendon loading during exercise protocols have not been reported. Only a few studies have attempted to evaluate the mechanical strength of exercised tendons. The long term effect of exercise on tendons appears to be positive, but researchers have suggested that periods of mechanical weakness occur in tendons during adaptation to loading conditions. Studies documenting changes associated with the terminal state of pathological tendons are also summarised. Unfortunately, there are no descriptions of tendon tissue in the early stages of overuse injury. Since blood flow is commonly implicated in the emergence of tendinitis, the final section covers recent work on blood flow and tendon physiology. Related research identifying cellular mediators (hyperthermia, hypoxia, and oxidative stress) involved in the development of tendinitis is also presented. Suggestions for further research into exercise loading and the development of tendon overuse injuries are made.