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The pathogenesis of tendinopathy: balancing the response to loading

Nature Reviews Rheumatology volume 6, pages 262–268 (2010)Cite this article

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Abstract

Tendons are designed to withstand considerable loads. Mechanical loading of tendon tissue results in upregulation of collagen expression and increased synthesis of collagen protein, the extent of which is probably regulated by the strain experienced by the resident fibroblasts (tenocytes). This increase in collagen formation peaks around 24 h after exercise and remains elevated for about 3 days. The degradation of collagen proteins also rises after exercise, but seems to peak earlier than the synthesis. Despite the ability of tendons to adapt to loading, repetitive use often results in injuries, such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water, hypervascularization and disorganized collagen fibrils. At the molecular level, the levels of messenger RNA for type I and III collagens, proteoglycans, angiogenic factors, stress and regenerative proteins and proteolytic enzymes are increased. Tendon microrupture and material fatigue have been suggested as possible injury mechanisms, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy.

Key Points

  • Tendons are metabolically active and respond readily to both loading and unloading

  • Mechanical loading results both in protein synthesis and degradation of collagen

  • Without sufficient rest (24 h) after exercise, net loss of collagen might occur that leaves the tendon vulnerable to injury

  • Tendinopathy is associated with neovascularization, but newly formed blood vessels (and nerves) disappear during healing

  • The pathogenesis of tendinopathy can be accelerated by overloading

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Figure 1: The different hierarchical levels (tendon–molecule) of the human Achilles tendon.
Figure 2: Schematic representation of collagen synthesis and degradation.
Figure 3: Response of collagen to loading.

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Article 07 January 2021

Neal L. Millar, Karin G. Silbernagel, … Scott A. Rodeo

Change history

  • 09 April 2010

    In the version of this article initially published online, the tendon in Figure 1 was indicated as being 0.5–1.0mm2 instead of 0.5–1.0cm2. In addition, the measurements relating to the collagen fascicle, fibril and molecule in Figure 1 should all refer to the diameter of these entities. These errors have been corrected in all versions of the article.

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  1. Institute of Sports Medicine, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, Bispebjerg Hospital, Building 8, University of Copenhagen, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark

    S. Peter Magnusson, Henning Langberg & Michael Kjaer

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  1. S. Peter Magnusson
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Correspondence to Michael Kjaer.

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Magnusson, S., Langberg, H. & Kjaer, M. The pathogenesis of tendinopathy: balancing the response to loading. Nat Rev Rheumatol 6, 262–268 (2010). https://doi.org/10.1038/nrrheum.2010.43

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