In Dr. Virginia Byers Kraus’ research specialty, treatment of the degenerative joint disease osteoarthritis, salamanders are not exactly the first thing that come to mind. And yet the lizard-like amphibian has provided some major inspiration for her work.
The salamander is one of several animals that have robust regenerative abilities to reproduce severed limbs. But this regeneration happens far more efficiently at the animal’s remote reaches, with limitations on injuries closer to its core. And it just so happens that damaged human joints can regenerate cartilage in a process that is far more effective at the body’s extremities.
As explained by Kraus, Mary Bernheim Distinguished Professor of Medicine, in a study published this year in the peer-reviewed journal Science Advances, it’s a process controlled by ribonucleic acid (RNA) molecules. There are 69 different small RNAs in human joints, which Kraus likens to instruments in a symphony individually tuning up in a normal ankle. But if a stressor happens, osteoarthritis or injury, it’s like a conductor tapping the podium to initiate repair sequences through these "instruments," these specific small RNAs.
“It turns out that ankles are very good at regenerating cartilage, while hips are very poor and knees are somewhere in between,” says Kraus, who is also an affiliate of the Duke Regeneration Center. “In osteoarthritis, ankle cartilage turns on the same repair pathway as limb-regenerating organisms like salamanders, done with small RNA molecules, and we now know which ones are responsible for a good repair response. So we’re figuring out how to get other joints to follow the same pattern or how to inject them to create a repair response in joints that need it.”
This comes in the wake of another major finding Kraus published in Science Advances last year, about a National Institutes of Health-sponsored study of the “osteoarthritis pathophysiological continuum” that can be revealed by blood tests. Using molecular biomarkers, these tests can detect osteoarthritis up to eight years before it can be detected with X-rays. Such knowledge can encourage at-risk patients to pursue healthier weight, diet and exercise habits to stave off complications and X-ray changes of the joint for as long as possible.
“I like the idea that the work on biomarkers and cartilage repair dovetail,” says Kraus. “I’m optimistic that over the next decade, we’ll see major advancement in the treatment of osteoarthritis. A number of drug companies already have different agents in the pipeline, and a lot of people in the field are on the verge of major breakthroughs.”