Using radiocarbon dating as a forensic tool, researchers have found that human cartilage rarely renews in adulthood. The study, published in the 6 July issue of Science Translational Medicine, suggests that joint diseases may be harder to treat than previously thought.
The dating technique reveals that cartilage is an essentially permanent tissue in healthy and osteoarthritic adults alike. The findings present new challenges for treating osteoarthritis and other joint diseases, and may redirect efforts to preventing injury and protecting joints from further damage.
Mass spectrometer measurements provide carbon-14 dates for cartilage, fat, and other body tissues. | Jan Heinemeier and Mette Horsleth
"The fact that you don't have renewal explains why it's so difficult to heal cartilage or to make it good again," said Michael Kjaer from the University of Copenhagen, Denmark, co-author of the study. "Once you have a damaged cartilage, one should not have too much hope of getting a renewal of it."
Researchers have debated whether cartilage, the tissue lining the surface of joints, regenerates or remains "fixed" throughout life, and little is known about the effects of joint diseases on cartilage turnover.
In the United States, more than 700,000 knee replacement surgeries are performed annually, according to the Centers for Disease Control and Prevention. The average cost for a total knee replacement procedure is about $30,000, according to a study by The Blue Cross Blue Shield Association.
"The special thing about the cartilage is that once you get an injury, there doesn't seem to be a good potential for regeneration. The question now is what is happening? Is there a very, very slow turnover of the tissue that can't be influenced?" said Kjaer.
To answer this question, Kjaer and colleagues turned to the bomb pulse method, which exploits the fact that all living things through their diet incorporate carbon-14 from the atmosphere. Atmospheric levels of this carbon isotope spiked due to the testing of nuclear bombs during the Cold War, leaving a detectable imprint in all organisms living at the time.
The technique has been used to estimate the age of the heart, fat, muscle, and other tissues. Kjaer and his colleagues applied it to cartilage in knee joints from eight healthy and 15 osteoarthritic individuals born between 1935 and 1997.
Across all individuals, the researchers detected virtually no formation of new collagen in cartilage, even in diseased knees, suggesting that the tissue is an essentially permanent structure.
Successful cartilage transplantation has been one significant challenge in knee joint surgery. | Jan Heinemeier and Mette Horsleth
Cartilage renews through adolescence, said Kjaer, but "you're left with what you have after you're 16 [years old]."
Previous studies have suggested that injury may spur cartilage to self-repair. "That speculation can now be totally abolished by this data. They show that the tissue turnover is not larger in people with osteoarthritis," said Kjaer.
The findings help explain the limited success of cartilage transplant and stem cell therapy for osteoarthritis.
"For many years, people have tried to do transplantation of cartilage and it's been very, very difficult," said Kjaer. "The fact the tissue is not very good at renewing is a challenge for transplantation therapy. And if you imagine now that you will give substances to make cartilage grow, drugs to stimulate cells to grow new cartilage, it will not do so."
"So we're basically back to prevention," said Kjaer, who noted that developing strategies for predicting patients' risk of developing a joint injury should be a priority. "If we could measure and detect the quality of the cartilage, maybe we can come in at an early stage" to prevent injury in the first place, he said.