October 2019

Humans, Like Salamanders, Can Regrow Joint Cartilage

Cartilage in human joints can repair itself through a process like that used by creatures such as salamanders and zebrafish to regenerate limbs, researchers at Duke University Health System (Duke Health), Durham, NC, found. In their article, published online in the journal Science Advances, the researchers identified a mechanism for cartilage repair that appears to be more robust in ankle joints and less so in hips. The finding could potentially lead to treatments for osteoarthritis, they said.

“We believe that an understanding of this ‘salamander-like’ regenerative capacity in humans, and the critically missing components of this regulatory circuit, could provide the foundation for new approaches to repair joint tissues and possibly whole human limbs,” said senior author Virginia Byers Kraus, MD, PhD, a professor in the departments of medicine, pathology and orthopedic surgery at Duke University School of Medicine.

Kraus and colleagues 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 was in the body. Cartilage in ankles is young, it’s middle-aged in the knee, and it’s 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 finding also helps explain why injuries to people’s knees and, especially, hips take a long time to recover and often develop into arthritis while ankle injuries heal quicker and less often become severely arthritic.

The researchers further learned that molecules called microRNA regulate this process. MicroRNAs are more active in animals that are known for limb, fin, or tail repair, including salamanders, zebrafish, African freshwater fish, and lizards. 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 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. The researchers said microRNAs could be developed as medicines that might prevent, slow, or reverse arthritis.

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