Humans have the salamander-like ability to regenerate cartilage in joints.

It is known that some animals, such as zebrafish, bichir, and axolotl, with a high regenerative capacity, regulate limb regeneration by a circuit of microRNA. Unlike these animals, humans cannot regenerate whole limbs and are also believed to be unable to counteract the breakdown or damage of cartilage and the development of osteoarthritis. Now, a study from Duke University shows cartilage in human joints can repair itself through a process similar to that used by salamanders and zebrafish to regenerate limbs. The team states they identified a mechanism for human cartilage repair that is more robust in ankle joints and less so in hips. The opensource study is published in the journal of Science Advances.

Previous studies have shown for animals with the capacity of whole-limb regeneration, blastema formation at the site of limb injury is critical. Also called Regeneration Bud, a blastema is a mass of undifferentiated cells with the capability to develop into an organ or a limb. Most recently, an important blastema miRNA regulatory circuit shared by three highly regenerative animal systems has been shown to control limb regeneration. The current study investigates whether miRNA, critical for blastema formation during limb regeneration across species, plays a role in articular cartilage protein turnover in humans.

The current study extracts RNA from the human ankle, knee, and hip cartilages to assess whether humans share any of the evolutionarily conserved miRNA essential for limb regeneration in highly regenerative animals. The group devised a way to test for regeneration by determining the age of proteins, and by extension the cartilage they form, based on how many conversions their amide group has gone through, also known as deamidation. Results show newly created proteins in tissue have few or no amino acid conversions, whereas older proteins have many; with this cartilage regeneration regulated by microRNA.

Data findings show the age of cartilage largely depends on where it resides in the body; cartilage in ankles is young, it’s middle-aged in the knee and old in the hips. The lab states this correlates with how limb repair occurs in certain animals, which more readily regenerate at the ends of legs or tails. They go on to add that they quantified the blastema-relevant miRNA, namely miR-21, miR-31, and miR-181c, expression in cartilage, with miR-21 shown to be the most highly expressed miRNA of the three.

The team surmises they have successfully profiled the regional patterns of protein turnover and miRNA expressions responsible for human joint cartilage regeneration. For the future, the researchers state that an understanding of this ‘salamander-like’ regenerative capacity in humans could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs.

Source: Duke University Medical Center

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