Humans are just not as good at some things as other animals – take, for example, limb regeneration. Salamanders are masters of regrowth, growing entire limbs and even parts of their organs with relative ease. Now it seems, we have a subtle 'inner salamander’ capacity, as the authors call it, to repair cartilage.
The Duke University team found that the process for cartilage repair is similar to that used by salamanders and zebrafish to regrow damaged or missing limbs. Interestingly, they found that cartilage is oldest in the hips of humans, youngest in the ankles, and middle-aged in the knees.
"We were very surprised to find that the repair capability was different in different joints," senior author Virginia Byers Kraus, a professor at Duke University Medical School, told IFLScience. "The traditional view has been that cartilage lining the joints throughout the body is all the same. In fact, even though all cartilages share some proteins, each joint has its particular set of cartilage proteins. On top of this, as shown in our study, now we understand that even the repair capacity differs in different joints."
The age of cartilage in different regions of the body parallels that of regenerative animals, whose regrowth capacity tends to be highest at the tips of their body, such as their legs or tails. The cartilage age may also help explain why hips take longer to recover than ankles and often develop arthritis.
Published in Science Advances, the team analyzed the molecular clock of amino acids to determine the age of proteins. Young proteins have no amino acid conversions whereas older proteins have many. They then used mass spectrometry to estimate protein turnover and tissue repair.
"The fact that older protein forms accumulated in the hips, but that 'middle-aged’ proteins predominated in the knees, and ‘young’ proteins in ankles tells us that the turnover of cartilage proteins is low in the hip, moderate in knees and high in ankles," said Kraus. "High protein turnover, as in the ankle joints, is a sign of a strong tissue repair response."
MicroRNA was found to regulate the repair of cartilage – again similar to salamanders and lizards. Activity of MicroRNA was highest in the ankles compared to the hips and knees.
"We were excited to learn that the regulators of regeneration in the salamander limb appear to also be the controllers of joint tissue repair in the human limb," lead author Ming-Feng Hsueh said. "We call it our 'inner salamander' capacity."
The team hope such knowledge of our inner biology could one day lessen or prevent arthritis. They are a long way away from making such claims now, but the study provides tantalizing possibilities for the future.
"We suggest that injection of regenerative miRNA into joints might be used in future to boost the innate repair capacity of the human joint to the level necessary to prevent osteoarthritis, for instance after a joint injury, or slow or reverse osteoarthritis once it has started," said Kraus.
"Osteoarthritis is a serious disease and the most common arthritis worldwide. Currently the only drug treatments relieve pain, not the disease process itself. There is a very great need for strategies to prevent, slow and reverse the process. These insights provide many avenues for further research in the quest for cures for this serious condition."