A small tweak to genes may finally enable us to regrow cartilage

As stated in the release, cartilage injuries to joints such as knees, shoulders, and hips can prove extremely painful and debilitating. Cartilage degeneration may cause arthritis and temporomandibular joint disorder. Patients with these illnesses gradually endure more pain and discomfort.

β-catenin is crucial for cells

It was previously considered that the Wnt signal transduction pathway determined whether a cell became bone or cartilage. β-catenin is the master factor that converts Wnt signals. The fact that when β-catenin was disturbed, bone turned into cartilage was the basis for this idea. However, β-catenin also acts as a cell adhesion molecule to facilitate cell-cell interaction – the original function identified prior to the discovery of its role in Wnt signaling. 

“We know that this molecule is important for cell fate determination, but the mechanism remained open to study,” said Dr. Hsu.

The researchers tested what would happen if β-catenin's signaling capacity was only partially compromised, and they discovered that, in that situation, the cells were unable to develop into bone or cartilage. Following these experiments, the researchers came to the conclusion that while Wnt signaling is a factor in bone creation, it is insufficient for cartilage production.

“We wanted to know what the factor was for cell fate determination,” said Dr. Maruyama. “What reprograms a cell to become cartilage if it isn’t Wnt signaling?”

The second major discovery: GATA 3

Skeletal cell fate flipping is caused by an alternate function of β-catenin. GATA3 is a single gene regulator that activates the expression of genes unique to cartilage in cells.

“GATA3 binds to the genome sequences required for the reprogramming. GATA3 is a game changer because we can use it to potentially change any somatic cell to become a cartilage-forming cell, similar to using four stem cell factors to generate embryonic stem cell-like cells called induced pluripotent stem cells (iPSC),” adds Dr. Hsu.

Controlling cell fate in this way allows researchers to order a cell to become bone, cartilage, or fat, which has huge implications for developing novel treatments for the 1 in 4 people who suffer from cartilage injuries and deterioration. There is no treatment that can regenerate cartilage at the moment, and present treatments are incapable of improving joint function.

This groundbreaking study in tissue regeneration has great hope for thousands of patients and presents fresh research directions for experts to investigate.