Tendon healing is a complex and highly-regulated process that is initiated, sustained and eventually terminated by a large number and variety of molecules. Growth factors represent one of the most important of the molecular families involved in healing, and a considerable number of studies have been undertaken in an effort to elucidate their many functions. This review covers some of the recent investigations into the roles of five growth factors whose activities have been best characterised during tendon healing: insulin-like growth factor-I (IGF-I), transforming growth factor beta (TGFbeta), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). All five are markedly up-regulated following tendon injury and are active at multiple stages of the healing process. IGF-I has been shown to be highly expressed during the early inflammatory phase in a number of animal tendon healing models, and appears to aid in the proliferation and migration of fibroblasts and to subsequently increase collagen production. TGFbeta is also active during inflammation, and has a variety of effects including the regulation of cellular migration and proliferation, and fibronectin binding interactions. VEGF is produced at its highest levels only after the inflammatory phase, at which time it is a powerful stimulator of angiogenesis. PDGF is produced shortly after tendon damage and helps to stimulate the production of other growth factors, including IGF-I, and has roles in tissue remodelling. In vitro and in vivo studies have shown that bFGF is both a powerful stimulator of angiogenesis and a regulator of cellular migration and proliferation. This review also covers some of the most recent studies into the use of these molecules as therapeutic agents to increase the efficacy and efficiency of tendon and ligament healing. Studies into the effects of the exogenous application of TGFbeta, IGF-I, PDGF and bFGF into the wound site singly and in combination have shown promise, significantly decreasing a number of parameters used to define the functional deficit of a healing tendon. Application of IGF-I has been shown to increase in the Achilles Functional Index and the breaking energy of injured rat tendon. TGFbeta and PDGF have been shown separately to increase the breaking energy of healing tendon. Finally, application of bFGF has been shown to promote cellular proliferation and collagen synthesis in vivo.

Tendinopathy is a broad term encompassing painful conditions occurring in and around tendons in response to overuse. Recent basic science research suggests little or no inflammation is present in these conditions. Thus, traditional treatment modalities aimed at controlling inflammation such as corticosteroid injections and nonsteroidal antiinflammatory medications (NSAIDS) may not be the most effective options. We performed a systematic review of the literature to determine the best treatment options for tendinopathy. We evaluated the effectiveness of NSAIDS, corticosteroid injections, exercise-based physical therapy, physical therapy modalities, shock wave therapy, sclerotherapy, nitric oxide patches, surgery, growth factors, and stem cell treatment. NSAIDS and corticosteroids appear to provide pain relief in the short term, but their effectiveness in the long term has not been demonstrated. We identified inconsistent results with shock wave therapy and physical therapy modalities such as ultrasound, iontophoresis and low-level laser therapy. Current data support the use of eccentric strengthening protocols, sclerotherapy, and nitric oxide patches, but larger, multicenter trials are needed to confirm the early results with these treatments. Preliminary work with growth factors and stem cells is promising, but further study is required in these fields. Surgery remains the last option due to the morbidity and inconsistent outcomes. The ideal treatment for tendinopathy remains unclear.

No abstract

Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the ''dose'' of load to the tendon enthesis -including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.

Background/hypothesis: Shoulder pain in elite swimmers is common, and its pathogenesis is uncertain. Hypothesis/study design: The authors used a crosssectional study design to test Jobe's hypothesis that repetitive forceful swimming leads to shoulder laxity, which in turn leads to impingement pain. Methods: Eighty young elite swimmers (13-25 years of age) completed questionnaires on their swimming training, pain and shoulder function. They were given a standardised clinical shoulder examination, and tested for glenohumeral joint laxity using a non-invasive electronic laxometer. 52/80 swimmers also attended for shoulder MRI. Results: 73/80 (91%) swimmers reported shoulder pain. Most (84%) had a positive impingement sign, and 69% of those examined with MRI had supraspinatus tendinopathy. The impingement sign and MRIdetermined supraspinatus tendinopathy correlated strongly (r s =0.49, p<0.00001). Increased tendon thickness correlated with supraspinatus tendinopathy (r s =0.37, p<0.01). Laxity correlated weakly with impingement pain (r s =0.23, p<0.05) and was not associated with supraspinatus tendinopathy (r s =0.14, p=0.32). The number of hours swum/week (r s =0.39, p<0.005) and weekly mileage (r s =0.34, p=0.01) both correlated signifi cantly with supraspinatus tendinopathy. Swimming stroke preference did not. Conclusions: These data indicate: (1) supraspinatus tendinopathy is the major cause of shoulder pain in elite swimmers; (2) this tendinopathy is induced by large amounts of swimming training; and (3) shoulder laxity per se has only a minimal association with shoulder impingement in elite swimmers. These fi ndings are consistent with animal and tissue culture fi ndings which support an alternate hypothesis: the intensity and duration of load to tendon fi bres and cells cause tendinopathy, impingement and shoulder pain.

Tendinopathy is a multifactorial spectrum of tendon disorders that affects different anatomical sites and is characterized by activity-related tendon pain. These disorders are common, account for a high proportion (∼30%) of referrals to musculoskeletal practitioners and confer a large socioeconomic burden of disease. Our incomplete understanding of the mechanisms underpinning tendon pathophysiology continues to hamper the development of targeted therapies, which have been successful in other areas of musculoskeletal medicine. Debate remains among clinicians about the role of an inflammatory process in tendinopathy owing to a lack of clinical correlation. The advent of modern molecular techniques has highlighted the presence of immune cells and inflammatory mechanisms throughout the spectrum of tendinopathy in both animal and human models of disease. Key inflammatory mediators - such as cytokines, nitric oxide, prostaglandins and lipoxins - play crucial parts in modulating changes in the extracellular matrix within tendinopathy. Understanding the links between inflammatory mechanisms, tendon homeostasis and resolution of tendon damage will be crucial in developing novel therapeutics for human tendon disease.

No abstract

This study provides evidence for an inflammatory cell infiltrate in early mild/moderate human tendinopathy. In particular, the authors demonstrate significant infiltration of mast cells and macrophages, suggesting a role for innate immune pathways in the events that mediate early tendinopathy. Clinical Relevance Further mechanistic studies to evaluate the net contribution and hence therapeutic utility of these cellular lineages and their downstream processes may reveal novel therapeutic approaches to the management of early tendinopathy.