Lizards May Help Treat Millions with Osteoarthritis – But How? New Study Shows

Experts from the Keck School of Medicine of USC have unveiled the intricate dynamics between two specific cell groups enabling lizards to grow back their tails.

The findings, shared today in Nature Communications, with support from the National Institutes of Health, delve into the exceptional capability of lizards to regenerate cartilage, replacing bone in the tails they lose.

This breakthrough might pave the way for therapeutic strategies aimed at repairing human cartilage impaired by osteoarthritis, a condition affecting approximately 32.5 million adults in the U.S., as estimated by the Centers for Disease Control and Prevention. As of now, no treatment exists for osteoarthritis.

Assistant Professor Thomas Lozito of the Keck School of Medicine of USC, the leading author of the study, remarked, “Lizards are kind of magical in their ability to regenerate cartilage because they can regenerate large amounts of cartilage and it doesn’t transition to bone.”

Lizards stand out as one of the few higher vertebrates capable of regenerating cartilage without ossification. Unlike humans, who lose the ability to mend damaged cartilage as they age, lizards can regenerate a limb encompassing multiple tissue types.

By studying organisms with enhanced healing abilities, researchers might uncover methods to mimic these restorative processes in mammals.

“The dream is to find a way to translate that process in humans because they cannot repair cartilage,” added Lozito. “This represents an important step because we need to understand the process in great detail before we can try to recreate it in mammals.”

What cells are involved in lizard cartilage regeneration?

Ariel Vonk, a PhD student in the Lozito Lab, along with her colleagues, found that fibroblasts, tissue-building cells, are essential in constructing cartilage in the lizard’s renewed tail. The study mapped out the transformation in gene activity within particular fibroblast cells that facilitated the formation of cartilage.

Additionally, they identified that septoclasts, a form of immune cell, played a pivotal role in warding off fibrosis or scarring, thus making regeneration possible.

Lozito emphasized the role of both cell types in initiating the regenerative pathway and highlighted that, unlike lizards, human tissues often form scars that hinder regeneration.

“Those two cell types working together laid the foundation for the beginning of the regenerative process.”

The next step, Lozito suggested, would be to explore single-cell RNA sequencing to pinpoint the molecular mechanisms that prevent scarring in lizards, with an aim to reproduce the process in mammals.

Can humans replicate the cartilage regeneration process of lizards?

Based on their understanding of the involved cells and molecular functions, the research team conducted experiments to see if they could mimic the cartilage-rebuilding process in lizard limbs, which typically don’t regenerate after loss.

By extracting septoclasts from lizard tails and implanting them into limbs lacking pro-regenerative immune cells known to suppress scarring, they managed to successfully trigger cartilage construction by simulating a tail-like signaling environment.

They are now optimistic about testing these methods on mammals, starting with mice, and applying what they learned from lizard limbs, Lozito concluded.

Source: 10.1038/s41467-023-40206-z

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