Like the axolotls
Signs of regeneration were found in the cartilages of adults
Polina Loseva, N+1
American researchers have found traces of tissue renewal in human leg joints. They measured the age of extracellular proteins in articular cartilage and noticed that the farther the joint is from the spine, the more young, newly formed proteins there are in it. In addition, scientists found increased expression of microRNAs in the regenerating tissue, which are found in animals capable of regeneration – for example, axolotls. The study was published in the journal Science Advances (Hsueh et al., Analysis of “old” proteins unmasks dynamic gradient of cartage turnover in human limbs).
Compared to fish and amphibians, most mammals have lost the ability to regenerate limbs. People can regrow newly amputated fingertips, but only in early childhood. However, even damaged skeletal tissues do not regenerate in adults, for example, with osteoarthritis – at least, it was thought so until now.
A group of scientists from Duke University Medical School led by Virginia Kraus decided to measure the age of individual molecules in the extracellular substance of cartilage. It is known that outside of cells, some amino acids in proteins undergo random non-enzymatic hydrolysis. As a result, amides turn into acids, and glutamine and asparagine form glutamate (glutamic acid) and aspartate. By the ratio of aspartate to asparagine, the lifetime of a particular protein site can be estimated.
The researchers worked with samples of healthy and affected cartilage tissue. They received healthy tissue after operations related to injuries, and the affected tissue from patients with osteoarthritis, in total they collected 18 different samples. Scientists measured the age of various extracellular proteins – collagen, aggrecan, fibronectin and others – and noticed that in the distal joints (ankle) proteins are younger than in the proximal (femoral).
Scientists have suggested that the different rate of recovery of extracellular proteins is a manifestation of the ability to regenerate, which is partially preserved in the distal parts of the limb and disappears in the proximal. Then, when the joint is destroyed, which accompanies osteoarthritis, the same regeneration processes should be started in the cartilages.
To test their hypothesis, the researchers measured the expression of characteristic microRNAs in cartilage tissue that were previously found in other animals with high regeneration abilities – the axolotl and the danio-rerio fish. In the samples with osteoarthritis, the concentration of these microRNAs was twice as high as in healthy cartilage, and in the ankle – two to five times more than in the shoulder, depending on the type of microRNA.
Thus, scientists have confirmed that under conditions of stress and tissue destruction, the same processes are triggered in human cartilage as in regenerating amphibian limbs and fish fins. They work more actively in the distal parts, and perhaps this explains why osteoarthritis is less common in the ankle than in the hip joint. The researchers do not exclude that the stimulation of these regeneration processes – perhaps the injection of the corresponding microRNAs – will allow in the future to better restore damaged articular cartilage.
Scientists believe that osteoarthritis is a very ancient disease, and probably appeared in fish, along with the first real joints. However, the mechanisms of its occurrence have never been studied until now, and researchers have, for example, to specifically damage the knees of sheep in order to follow its development.
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