Tendinopathy—from basic science to treatment

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Abstract

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy.

Key Points

  • Tendon disorders are common, often under-reported and a major clinical problem

  • Most current treatments for tendinopathy are neither effective nor evidence-based

  • Molecular processes underlying tendinopathy are now being elucidated: metalloproteinase enzymes are thought to have a key role in the regulation of the activity of tendon cells and matrix remodeling in both normal and pathologic tendon

  • The potential roles of neuropeptides, inflammatory mediators and mechanical strain (either too much or too little) acting on the resident tenocytes are the source of some controversy and require in-depth investigation using in vitro and in vivo models

  • Excessive or inappropriate activity of destructive matrix-degrading enzymes might be a novel therapeutic target for tendinopathy; other treatments in development include the injection of stem cells, gene therapy and tissue engineering to repair or replace damaged tendon tissue

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Figure 1: Schematic of tendon structure and composition.
Figure 2: Major structural and molecular changes in chronic tendinopathy.

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Acknowledgements

The author would like to acknowledge all members of the Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, past and present, who have contributed so much to his studies on tendon pathology over the years. He would also like to thank all his collaborators, in addition to the surgeons, physicians and scientists who have provided materials and technical and intellectual support. His work would also have been impossible without the financial support of many funding agencies: in particular, the Arthritis Research Campaign, Action Medical Research, Dunhill Medical Trust, REMEDI, Rosetrees Trust, Elkin Charitable Foundation and the Isaac Newton Trust. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscapeaccredited continuing medical education activity associated with this article.

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G Riley has acted as a Consultant for Wyeth Pharmaceuticals.

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