Lizards, often associated with their fascinating ability to regrow tails, have now revealed an even more astonishing superpower – the ability to regenerate cartilage without transitioning to bone. A pioneering team of researchers from the Keck School of Medicine at the University of Southern California (USC) has unveiled the intricate interaction between two specific cell types that enables lizards to regenerate their tails and the cartilage within them. This breakthrough, funded by the National Institutes of Health and recently published in Nature Communications, holds immense promise for understanding and potentially recreating cartilage regeneration in humans, paving the way for treating osteoarthritis and other degenerative conditions.

Background

For the first time, scientists have delved into the biological processes that facilitate lizards' remarkable cartilage regeneration, which stands in stark contrast to humans' inability to regenerate cartilage once it's damaged, particularly in cases of osteoarthritis. Approximately 32.5 million adults in the United States suffer from osteoarthritis, a degenerative disease that currently lacks a cure, according to the Centers for Disease Control and Prevention.

Dr. Thomas Lozito, the corresponding author of the study and assistant professor of orthopaedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of USC, describes lizards as "magical" in their regenerative capabilities. Lizards can generate substantial amounts of cartilage, a tissue that remains cartilaginous and doesn't transform into bone. This extraordinary ability to regenerate cartilage without ossification is a scientific marvel that has far-reaching implications.

Fibroblasts

Ariel Vonk, a PhD student in the Lozito Lab and the first author of the study, identified a key player in this regenerative process – fibroblasts. These cells, known for their role in tissue construction, were found to be responsible for building cartilage in the lizard's regenerated tail. By examining gene activity changes within specific fibroblast cells, the researchers gained insights into the intricate mechanisms of cartilage reconstruction.

Another integral piece of the puzzle is a type of immune cell known as a septoclast. This immune cell was identified as crucial for inhibiting fibrosis, which is scarring of tissue that prevents regeneration. The harmonious interplay between fibroblasts and septoclasts lays the groundwork for the initiation of the regenerative process. Unlike lizards, human tissue tends to scar, obstructing the potential for tissue regeneration.

The study's findings highlight a groundbreaking avenue of research that could revolutionize human medicine. By understanding the mechanisms that prevent scarring and enable cartilage regeneration in lizards, researchers hope to recreate this process in mammals. Single-cell RNA sequencing is proposed as a tool to delve deeper into the molecular underpinnings of scarring prevention.

The research didn't stop at understanding – it delved into the realm of application. To test the acquired knowledge, the team embarked on a mission to induce cartilage regeneration in lizard limbs, which, unlike tails, do not regenerate naturally. By extracting septoclasts from lizard tails and implanting them into limbs, the researchers created a favorable environment that encouraged cartilage growth. The successful induction of cartilage building in a lizard limb offers a tantalizing glimpse into the potential for human cartilage regeneration.

Looking ahead, the researchers are enthusiastic about the possibility of replicating their experiments on mammalian models, starting with mice. With the newfound insights into the intricate dance of cells and molecular processes, the journey towards conquering cartilage-related ailments like osteoarthritis takes a significant stride forward. This groundbreaking research not only deepens our understanding of regenerative processes in nature but also brings us closer to unlocking the secrets of cartilage regeneration that could change the lives of millions.