Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb ¹⁴ C

Abstract

Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of 14C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of 14C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, 14C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C.

What is the impact of inflammation on the critical interplay between mechanical signaling and biochemical changes in tendon matrix?

“…Somewhat in contrast, acute exercise does not upregulate mRNA expression of collagen, or growth factors that stimulate collagen synthesis, in human patella tendon (14,40). Furthermore, a very recent study reveals that the core of the human Achilles tendon has almost no turnover in adult life (16), and earlier studies on human biceps tendon and on horse tendons provide further support for a low rate of tissue turnover in tendons (6,42). So the question still remains, whether human adult tendons in fact demonstrate any significant dynamics with regard to the primary collagen structure of the tendon when subjected to exercise.…”

Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue

“…This mechanism could explain the increased HP density in the young athletes. It is uncertain why this effect would be absent in aging master athletes, although it is known that age may blunt the LOX response possibly due to lack of tissue renewal associated to decline in tendon cell number and function with age (Nagy et al 1969;Heinemeier et al 2013;Thorpe et al 2010). …”

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

“…The ability of tendon tissues to bear these loads originates from a unique structural organization and adaptability of the tendon tissue in adjusting its load-bearing capacity [11]. Although tendon cells can reinforce tissue upon increased loading demand, net extracellular matrix synthesis in healthy tendons is low compared to other connective tissues [12,13]. Sudden exposure to elevated mechanical stresses can put tendon tissues at risk of damage, and overloading is widely considered to be a causative factor in the onset of tendinopathy [14][15][16].…”