Researchers have discovered, contrary to popular belief, that human joint cartilage can repair itself. It does it in a manner similar to that used by creatures such as zebrafish and salamanders. This finding could potentially lead to treatments for osteoarthritis which is the most common disorder of joints in the world.
The research team identified a mechanism for repair of cartilage that seems to be more robust in ankle joints and less so in hips. They believe that further understanding of this salamander like regenerative capacity in humans combined with the critically missing components of this regulatory circuit, might provide a foundation for new approaches for joint tissue repair and even whole human limbs.
The team created a way to determine the age of proteins through internal molecular clocks which are integral to amino acids. These amino acids convert one form to another with predictable regularity.
Proteins which are newly created in tissue have very few or no amino acid conversions. Older proteins actually have many. Through understanding this process, the team was able to use sensitive mass spectrometry to identify when key proteins found in human cartilage, including collagens, were young, middle aged or old.
The team discovered that cartilage age depends largely on where it resides in the body. Cartilage found in the ankles is young, middle aged in the knee and older in the hips. This correlation between the location of cartilage in the body and age aligns with how repair of limbs occurs in certain animals which more readily regenerates at the furthest tips such as the ends of tails and legs.
Additionally, the findings also explain why injuries to the knees and especially the hips, take a long time to heal and often times develop into arthritis. Ankle injuries typically heal much quicker and are less prone to becoming severely arthritic.
The team also learned that molecules which are known as microRNA regulate this process. These microRNAs are much more active in animals that are known for tail, fin or limb repair including zebrafish, salamanders, and African fresh water fish and lizards.
Humans also have these microRNAs…an evolutionary artifact which can provide humans the ability for repair of joint tissue. Similar to animals, microRNA activity is significantly different depending on its location. It is highest in ankles compared to the knees and hips and also higher in the top layer of cartilage as compared to deeper levels of cartilage.
The team explains that the regulators of regeneration in the limbs of salamanders appears to also be the controllers of repair of joint tissue in human limbs. They are calling it the “inner salamander” capacity. They believe microRNAs could be developed as treatments that might prevent, slow or even reverse arthritis.
They believe there is the ability to boost these regulators to fully regenerate cartilage that has degenerated in an arthritic joint. By figuring out what regulators are missing compared with salamanders, they may be able to add the missing components back and then develop a way to regenerate part or even all of an injured human limb. The team believes this is a fundamental mechanism for repair that could be applied not only to cartilage, but also many tissue types.
To view the original scientific study click below
Analysis of “old” proteins unmasks dynamic gradient of cartilage turnover in human limbs.
