Quirks & Quarks

Could we prevent arthritis by regenerating cartilage?

We seem to have an innate repair mechanism, like salamanders. We just need it to work much better.

We seem to have an innate repair mechanism, like salamanders. We just need it to work much better

A spotted salamander (Photo by Matthias Balk/dpa/AFP via Getty Images)

Investigating whether or not humans could regenerate the cartilage in our joints to prevent osteoarthritis might have been a pointless exercise.

But Dr. Virginia Byers Kraus just didn't believe the conventional wisdom. "We'd always been told that the collagen you're born with is the collagen you die with," she told Bob McDonald of Quirks & Quarks

But a new study by Dr. Byers Kraus and her team at the Duke University school of medicine has shown that humans can grow new collagen to rebuild damaged cartilage. 

Ultimately understanding how we do this could be the key to new treatments to prevent or repair the kind of cartilage damage that leads to osteoarthritis, and ultimately the accumulated damage that necessitates hip and knee replacements.

Few joints in the human body are immune to osteoarthritis (Virginia Byers Kraus, Ming-Feng)

Channelling your inner salamander

The inspiration for this work came originally from animals like salamanders and zebrafish, which are known to have the ability to regenerate tissue and even regrow limbs and fins. In doing so, they have to generate new collagen to form cartilage. 

This was a capacity thought to be missing in humans, possibly because our evolutionary ancestors lost this ability. As a result, all of the collagen in our bodies should be the same age. Byers Kraus and her team found out this was not the case.

Osteoarthritis in knee xray (Virginia Byers Kraus, Ming-Feng)

The age of collagen proteins in cartilage can be determined by looking at the random chemical changes that accumulate over time. Using mass spectrometry, Byers Kraus and her colleagues were able to examine the proteins in collagen from different parts of the human body. 

They found that collagen from the ankles appeared to be much younger than collagen from the knees, and collagen from the knees was in turn younger than collagen from the hips. This was clear evidence that new cartilage forms in humans, but it forms more frequently in the joints closest to the extremities.

It turns out this is the case in limb-regenerating animals like salamanders as well.

"We learned that the limb regenerating organisms can regenerate the furthest parts of their limb much better than the nearer parts," said Byers Kraus. "A foot regenerates better than a hip for instance with repeated limb amputations. And so that gave us a clue that perhaps some mechanism that was there in these limb regenerating organisms that were conserved over millions of years." 

Why the extremities regenerate better is probably simply evolutionary triage. An animal can potentially survive long enough to regenerate if it loses a toe or a foot. If a whole leg is taken, then not only is the animal not likely to survive the injury, it's less likely to survive the long period of disability required to regenerate such a substantial limb. As a result evolution would select for active repair at the extremities, but not closer to the core.

Osteoarthritis appears much less frequently in ankles than in knees and hips (Virginia Byers Kraus, Ming-Feng)

Ankles get injured more, develop osteoarthritis less

Humans have lost the ability to regenerate even small parts of our limbs, but this work suggests we seem to have retained the ability to do some minimal repair of our tissues — and that repair works best nearer the extremities. Byers Kraus suggest this explains why hips and knees seem so much more vulnerable to age-related arthritis than ankles.

"We already know that hips are twice as likely to get replaced as knees. We also did a study where we were looking for x-rays of the ankle, and we easily found many examples of very moderate osteoarthritis, but we had to screen ninety thousand x-rays to find examples of severe ankle osteoarthritis."

What do they have that we don't?

The key to this repair seems to be messenger molecules known as microRNA which are probably turning important genetic repair mechanisms on and off. Byers Kraus and her team identified several microRNA molecules known to regulate regeneration in salamanders, and looked to see if they were also present in human cartilage. They found the microRNA in humans, and also found that these molecules were more common in human ankles than in knees and hips.

This, in time, could be the key to developing osteoarthritis treatments that might stimulate these microRNA or the repair mechanisms they regulate, so that they operate more efficiently in areas where they are not active now. 

"We're hoping to try to get a more comprehensive understanding of the microRNA profiles in the human to determine if there's something that's critical that the Salamander has that we are missing." 


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