Arthritis clues in how lizards rebuild tails

Some lizards which lose their tails while evading predators can rebuild them and now scientists have identified two cell types that allow it to happen.

The cells are specifically involved in the process of cartilage regeneration, which replaces bone in the new tail, so the discovery could offer insights into recreating that process in humans.

This has important implications for the treatment of osteoarthritis, the most common form of arthritis in Australia. Osteoarthritis affects 1 in 5 people over the age of 45 and in 2019–2020 cost the Australian health system an estimated $3.9 billion.

The disease involves a breakdown of cartilage – a strong, flexible connective tissue that protects joints and bones – and mostly affects the hands, spine, hips, knees, and ankles.

“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,” explains Thomas Lozito, assistant professor of orthopaedic surgery, and stem cell biology and regenerative medicine at the Keck School of Medicine, the University of Southern California, USA. 

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A green anole lizard regenerating its tail. (Pic: Ariel Vonk/Lozito Lab)

“The dream is to find a way to translate that process in humans because they cannot repair cartilage,” adds Lozito, who is corresponding author of the new study, which has been published in Nature Communications.

“This [study] represents an important step because we need to understand the process in great detail before we can try to recreate it in mammals.”

The research team determined that fibroblasts, which help build connective tissue, are the critical cell type that builds cartilage in the lizard’s regenerated tail. They also described the gene changes that occur in certain fibroblasts to enable this process.

Cosmos lizards: Avoiding predation

Another type of immune cell, called a septoclast, was found to play an important role in preventing fibrosis, or scarring. This is important because, according to Lozito, a major difference between humans and lizards is that human tissue tends to scar, and this prevents tissue regeneration. 

Unlike tails, lizard limbs do not normally regenerate because they lack these septoclasts. However, the team was able to recreate the process and induce cartilage building by taking septoclasts from lizard tails and implanting them into the limbs.

Lozito says that a future avenue for research is to use single-cell RNA sequencing to better describe the molecular mechanisms that stop scarring in lizards. The team also hopes to test whether they can induce cartilage building in mammals, beginning with mice, using the techniques they used in their experiments on lizard limbs. 

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