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A theme of recent years is the discovery of processes of regrowth that operate in mammalian tissues long thought to be non-regenerative. In this case, researchers have found a mechanism of regeneration that operates in cartilage, albeit not to the degree that would be helpful for recovery from more serious injury or the wear of aging. Still, where a mechanism exists at all, it should be possible to find ways to enhance its operation. This work is interesting for the resemblance that this regenerative process bears to the way in which salamanders regrow lost organ tissue. Finding ways to bring that sort of exceptional regenerative capacity into mammals is the subject of numerous research programs.
Contrary to popular belief, cartilage in human joints can repair itself through a process similar to that used by creatures such as salamanders and zebrafish to regenerate limbs. The mechanism for cartilage repair appears to be more robust in ankle joints and less so in hips. The finding could potentially lead to treatments for osteoarthritis, the most common joint disorder in the world.
Researchers devised a way to determine the age of proteins using internal molecular clocks integral to amino acids, which convert one form to another with predictable regularity. Newly created proteins in tissue have few or no amino acid conversions; older proteins have many. Understanding this process enabled the researchers to use sensitive mass spectrometry to identify when key proteins in human cartilage, including collagens, were young, middle-aged or old. They found that the age of cartilage largely depended on where it resided in the body. Cartilage in ankles is young, it’s middle-aged in the knee and old in the hips. This correlation between the age of human cartilage and its location in the body aligns with how limb repair occurs in certain animals, which more readily regenerate at the furthest tips, including the ends of legs or tails.
The researchers further learned that molecules called microRNA regulate this process. Not surprisingly, these microRNAs are more active in animals that are known for limb, fin or tail repair, including salamanders and zebrafish. These microRNAs are also found in humans – an evolutionary artifact that provides the capability in humans for joint tissue repair. As in animals, microRNA activity varies significantly by its location: it was highest in ankles compared to knees and hips and higher in the top layer of cartilage compared to deeper layers of cartilage.
“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. We believe we could boost these regulators to fully regenerate degenerated cartilage of an arthritic joint. If we can figure out what regulators we are missing compared with salamanders, we might even be able to add the missing components back and develop a way someday to regenerate part or all of an injured human limb. We believe this is a fundamental mechanism of repair that could be applied to many tissues, not just cartilage.”
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