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 (14)C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of (14)C, produced by nuclear bomb tests in 1955-1963, which is reflected in all living organisms. Levels of (14)C 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 (14)C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of (14)C 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, (14)C 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.

Figure 1.

¹⁴C bomb-pulse curve. Concentration of ¹⁴C in atmospheric CO₂ (black line), shown as pMC (26). Testing of nuclear bombs from 1955 to 1963 nearly doubled the atmospheric levels of ¹⁴C, which was followed by an exponential decrease after the Test Ban Treaty in 1963. Measured levels of ¹⁴C are shown in relation to birth year for samples of human Achilles tendon (gray squares) and skeletal muscle (open circles) taken in year 2000. The levels of ¹⁴C found in the tendon tissue generally correspond to the atmospheric levels many years before sampling, thus indicating a very slow rate of tissue replacement. Skeletal muscle levels of ¹⁴C correspond to atmospheric levels ∼2 yr before the time of sampling (dashed arrow), thus indicating continuous tissue turnover, as essentially no memory of lifetime exposure to the bomb pulse remains in the muscle tissue.

Figure 2.

Model for human tendon tissue formation and turnover. Dotted line shows the 0–17 yr moving average of the ¹⁴C level in the atmosphere, representing the relation between calendar year and the average atmospheric ¹⁴C level during the subsequent 17 yr (e.g., value in 1960 corresponds to average atmospheric ¹⁴C between 1960 and 1977). The curve reproduces relatively well the observed levels of ¹⁴C in Achilles tendons samples (gray squares), suggesting that the tendon tissue ¹⁴C was incorporated during height growth (0–17 yr) and that tissue replacement during adulthood was very limited. The large black circle indicates three tendon samples with deviating ¹⁴C concentrations, potentially due to abnormally high turnover during later periods in life with low atmospheric ¹⁴C. The dataset contained three clear outliers, indicated as #25, #28, and #30.