According to the researchers, humans are believed to be unable to counteract repetitive joint use and injury. This is because the turnover of insoluble collagen – a key component of the connective tissues – is thought to be limited in human adult cartilage.
For their study, the researchers examined protein turnover in the cartilage found in the lower limb joints of humans. To do this, they determined the age of proteins using internal molecular clocks that are integral to amino acids. Newly-formed proteins have fewer amino acid conversions compared to older proteins.
The researchers found that the cartilage tends to be young in the ankles, middle-aged in the knee and old in the hips. This pattern is also found in animals with regenerative abilities, where regeneration usually happens more actively at the tips of the body, including the ends of legs or tails.
Further analysis showed that cartilage regeneration in humans is likely regulated by molecules called microRNAs. These molecules were previously found to be more active in animals known for limb, fin or tail regeneration, such as salamanders, zebrafish, African freshwater fish and lizards.
Human microRNA activity is highest in the ankles compared to the knees and hips and higher in the top layer of the cartilage compared to the deeper layers. This finding may help explain why ankle injuries heal quicker and rarely become severely arthritic compared to knee and hip injuries. The researchers said that regulators like microRNAs could be potential targets for preventing and treating osteoarthritis. (Related: Compound in horny goat weed can promote cartilage repair.)
“We believe we could boost these regulators to fully regenerate degenerated cartilage of an arthritic joint,” said corresponding author Virginia Kraus of the Duke University School of Medicine.
The next step is to determine the regulators in salamanders that are not present in humans. These missing components, in turn, can provide the foundation for new approaches to repair joint tissues and possibly the whole human limbs, according to Kraus.
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