The Biology of Tendon Pathology

Cy Frank, M.D., FRCSC
David Hart, PhD
The University of Calgary - McCaig Institute
Calgary, AB

Tendons and ligaments both belong to a family of 'dense connective tissues' that serve important roles in vivo in connecting functioning parts. Tendons connect muscles to bones and thus they serve to transmit very significant repetitive loads during joint motion. They also serve to stabilize joints during all activities in which both gravity and external loads must be overcome. Tendon structures and functions have been studied by many people. In this short article, we will review briefly some of what we consider to be a few highlights of tendon biology that would be of interest to orthopaedic surgeons.


Despite appearing to be 'simple', tendons are surprisingly complex and heterogeneous. As a principle, in order to resist the very high, repetitive loads that they must carry, tendons normally have a very high proportion of densely packed collagen fibres organized in a nearly parallel fashion, spaced by water. There are several types of collagen in tendons and the collagen is organized to carry both high loads and cross-linked in a way to resist fatigue failure from repetitive loads. There are several types of proteoglycans that bind water and help bridge between collagen fibres; serving important functions in transmitting loads and other biochemical signals between surprisingly inter-connected tendon cells. Tendons do have a blood supply (generally more near insertions and more on their surfaces) and they do have both nociceptive (pain) and proprioceptive (position sense) nerves in these same locations. Nerves and blood vessels clearly have important biological and physiological effects1.

Tendons have very complex insertion sites onto muscles at one end and into bones at the other end, with complicated transitions of their structures through a zone of fibrocartilage into mineralizing fibrocartilage before their fibres enter and are embedded in bone. The cells near and at the insertions are therefore different; likely modified by that local loading environment to produce different matrix that is needed to prevent damage and failure of the tendon at those very high stress locations.

Not all tendons are the same. As described by Gelberman and co-workers2, there are two big 'sub-families' of tendons: those with and those without a synovial covering. That synovial covering serves to lubricate interfaces but it also serves as a relative barrier to vascular and cellular in-growth. This has important implications for damage, for repair and for the healing of damaged tendons. They are not all equally likely to be damaged, nor are they equally likely to heal. This is well known in and around the hand, but it is also true with all other joints in the body.

Figure 1: A schematic depiction of the metabolic balance of cellular responses in tendons. Note that atrophy from immobilization and injury (either repetitive strain injury or sudden macro-injury) drive catabolic changes in cells and thus can create local matrix degradation.

Tendon fibroblasts are particularly sensitive to changes in tendon loading conditions; responding with metabolic changes in their synthesis and degradation of these very important matrix molecules that make up the functioning tendon. Load deprivation of a tendon is particularly damaging to the tendon matrix, dramatically decreasing matrix synthesis and increasing matrix degradation.

Interestingly, excessive tendon loading can also be damaging to a tendon, but this is certainly not a simple matter of breaking the collagen fibres and mechanically damaging the tendon matrix. Excessive loading can certainly fail the tendon matrix and cause loss of collagen load-carrying ability. Higher-than-normal loads may also, however, simply alter cellular expression within the tendon and, like the situation described above with immobilization; create an environment that favours high matrix turnover with a propensity to matrix degradation.

If there is enough load to drive enough gross local physical matrix damage, it can potentially trigger local inflammation (red/hot/tender/swollen changes locally) with secondary vascular in-growth and scar-like repair reactions. If loads are not that high or prolonged enough to cause gross collagen fatigue damage, matrix can apparently become damaged by local cellular processes without local secondary inflammatory changes. This process has been called 'tendinosis' (without local inflammation) as opposed to 'tendonitis' (with inflammation). These processes have been studied in both human biopsies and in animal models3 in an attempt to better understand the pathological causes signs, symptoms and mechanisms of 'tendinopathy' and to be able to propose more effective treatment and prevention strategies. Programmed cell death caused by high local matrix strains4 may be one cause of tendinopathy.

  1. Ackermann P.W., Salo P.T., Hart D.A. Neuronal pathways in tendon healing. Front Biosci. 2009 Jun 1;14:5165-87. Review.
  2. Boyer M.I., Gelberman R.H., Burns M.E., Dinopoulos H., Hofem R., Silva M.J. Intrasynovial flexor tendon repair. An experimental study comparing low and high levels of in vivo force during rehabilitation in canines. J Bone Joint Surg Am. 2001 Jun;83-A(6):891-9.
  3. Archambault J.M., Hart D.A., Herzog W. Response of rabbit Achilles tendon to chronic repetitive loading. Connect Tissue Res. 2001;42(1):13-23.
  4. Scott A., Khan K.M., Heer J., Cook J.L., Lian O., Duronio V. High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model. Br J Sports Med. 2005 May;39(5):e25.

Submit Community Content

If you have orthopedic information that you would like to share with the Orthogate Community, please register/login and submit your news, event, job, article, case or workshop from the Submit Content menu under the My Account area. Learn more!