Researchers from the Weizmann Institute and Kyoto University have found that human cartilage has about a third as many shock-absorbing molecules as other apes; a clue to one of the causes of our joint fragility, not a medical diagnosis
Human joints often wear down over time, while other great apes rarely suffer from similar joint diseases without serious injury. A study published in Nature suggests a possible evolutionary explanation: a change in the control of genes responsible for producing molecules that help cartilage absorb shock.
The work was led by Dr. David Gokhman and Nadav Mishol of the Weizmann Institute of Science, in collaboration with Dr. Fumitaka Inoue and Yizhi Yan of Kyoto University and other colleagues. To identify meaningful differences in skeletal function, the researchers went beyond comparing DNA sequences between humans and other great apes.
Hundreds of thousands of differences, a small percentage that has an impact
The team mapped about half a million single-letter changes in DNA that distinguish humans from chimpanzees. Using tests of regulatory sequence activity, they estimated that only about 3% of the changes they examined affected gene activity during skeletal cell development. The researchers also created hybrid stem cells containing the genomes of a human and a chimpanzee or gorilla in the same cell, and grew them into cells involved in bone and cartilage development. This way, they compared the activity of the sequences in a shared cellular environment.
The missing component in human cartilage
One of the most striking results was the relatively low activity of a group of genes involved in the formation of glycosaminoglycans (GAGs): long molecules that bind water and help cartilage maintain its flexibility and ability to absorb loads. Examination of tissue from various joints found that the amount of this substance in human cartilage was about a third of that measured in the cartilage of chimpanzees, gorillas, orangutans and bonobos.
The finding suggests a possible link between an evolutionary change in cartilage composition and a human tendency to wear out joints. However, researchers cannot yet conclude from it what will happen to a particular person's knees, nor can all cases of osteoarthritis be attributed to a single mechanism. Age, loads, injuries and other factors also play a role.
The researchers offer two possibilities, both still speculative, to explain the change: it may have evolved alongside cartilage changes that aided brain activity, and it may have been part of the adaptations to a thin skeleton and long-distance movement. Further studies will be needed to examine why the trait was selected and how this knowledge can be used for prevention or treatment.
Questions and Answers
Has the single gene responsible for joint wear and tear been found?
No. The researchers identified differences in the activity of a group of genes and in the composition of cartilage, but joint wear is influenced by many factors.
Has it been proven that walking upright has caused a change?
No. This is a possible evolutionary explanation that requires further examination, not direct proof of why the change evolved.
Is there now a test or treatment based on the discovery?
Not yet. This is basic research in comparative cells and tissues.
The scientific article
Source: Announcement from the investigating institution.
