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Understanding tendinopathies
  1. A Scott,
  2. V Duronio
  1. University of British Columbia, Vancouver, BC, Canada; ascott{at}interchange.ubc.ca

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    We commend Professor Murrell for making a major novel contribution to the understanding, and thus potentially the treatment, of chronic tendinopathies.1 He has shown in patients with supraspinatus tendinopathy that a substantial portion of the cellular compartment of the tendon shows nuclear fragmentation, a key characteristic of apoptosis.2

    Does Professor Murrell feel that apoptosis would necessarily be a “harmful” pathological event in tendon or might there be an optimal, basal level of apoptosis? We appreciate that excessive apoptosis—programmed cell death—is a feature of degenerative pathologies such as muscular dystrophy and Alzheimer’s disease.3 In these conditions apoptosis may contribute to deterioration of the diseased tissue. On the other hand, it is a characteristic feature in physiological situations such as scar remodelling, in which coordinated death of myofibroblasts is a desirable outcome.4 A recent study does suggest that proliferation of tenocytes can enhance tendon remodelling, as proliferation of tenocytes after IGF-I injections was accompanied by improved tendon stiffness and reduced lesion in equine flexor tendinopathy.5 Other studies have shown fibroblast apoptosis from excessive strain6 or, paradoxically, decreased loading.7

    We would also appreciate Professor Murrell’s opinion on the significance of a third of tendon cells displaying a positive TUNEL assay, months after the onset of symptoms. Could apoptotic cells remain in tendon tissue for months after injury, or might the condition cause continual apoptosis and proliferation concurrently? If the latter were true, would apoptosis be a causal event of tendon degeneration or a secondary effect of scar remodelling? The fact that paratenonitis can directly cause tendinosis and loss of tenocytes suggests a possible causal role of apoptosis.8

    Does Professor Murrell see growth factors as playing a role in modulating apoptosis in the tendon, and could the effect of growth factors on tenocyte death and survival be tested in vitro or in model systems? Such investigations would be complicated by the many interacting conditions in the tendon which could promote or prevent apoptosis, including integrin mediated signals, soluble factors, and cellular stresses such as hypoxia and reactive oxygen species. The distinct phenotypes of tenocytes within and among tendons would add yet another layer of complexity to the story.

    Again, we commend Professor Murrell for this contribution. We will be very curious to know which caspases are activated in the supraspinatus and in other tendinopathies, and whether there would be an inhibitory effect of caspase inhibitors. By showing for the first time that nuclear fragmentation is a significant feature of tendinopathy, Professor Murrell has brought us one step closer to a more complete understanding of this condition.

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