Around 350 million individuals in the globe are dealing with cartilage deterioration or injury. Over time, patients with these illnesses feel increasingly uncomfortable and in pain. The possibility of significant treatment, however, comes from a promising development in tissue regeneration research. Researchers at The Forsyth Institute have proposed a novel method for producing cartilage cells, which might have far-reaching applications in the field of regenerative medicine for the treatment of cartilage injuries and degeneration in the future.
Cartilage injuries, especially to weight-bearing joints like the knees, shoulders, and hips, may be highly painful and debilitating, as any weekend warrior will agree. Arthritis and temporomandibular joint dysfunction (TMJ) are two of the most common causes of cartilage deterioration. Together, they impact 350 million individuals worldwide and cost the US healthcare system about $303 billion annually. The discomfort and agony felt by patients with these diseases tends to intensify over time.
New methods for producing cartilage cells are proposed in an interesting study headed by researchers at The Forsyth Institute. These findings have significant implications for the treatment of cartilage injuries and degeneration in the future, opening up new research avenues in regenerative medicine. Co-first authors Takamitsu Maruyama and Daigaku Hasegawa and senior author Wei Hsu describe two novel findings in their paper “GATA3 mediates nonclassical -catenin signaling in skeletal cell fate determination and ectopic chondrogenesis.” One of the findings is a new understanding of a multifaced protein called β-catenin.
Dr. Hsu teaches at Harvard’s Department of Developmental Biology and is a senior scientist at the Forsyth Insitute. His affiliation with the Harvard Stem Cell Institute is that of an affiliate faculty member. In addition to Jody Haigh and Maxime Bouchard of Canada and Tomas Valenta and Konrad Basler of Switzerland, the research team also comprised a number of other experts. This research was published in the most recent edition of Science Advances.
To learn how cartilage may be repaired, as Dr. Maruyama of Forsyth put it, was the motivation behind the study. The researchers set out to learn the mechanisms behind cell fate regulation, specifically how to direct a somatic cell to differentiate into cartilage rather than bone.
It was previously believed that the Wnt signal transduction pathway decided whether a cell developed into bone or cartilage. Wnt signals are primarily transduced by the master factor β-catenin. This theory is predicated on the observation that bone transformed into cartilage upon β-catenin disruption.
Although its significance in Wnt signaling was discovered later, β-catenin was first identified as a cell adhesion molecule to enable cell-cell contact. However, Dr. Hsu noted that the method by which this chemical plays a role in determining cell destiny was yet unknown.
Researchers examined what would happen if β-catenin’s signaling function was only slightly compromised and found that cells were unable to create bone or cartilage under those conditions. The results of these experiments led the researchers to the conclusion that Wnt signaling is necessary for the development of bone but not of cartilage.
A key component in determining cell destiny was of interest to Dr. Maruyama and his team. If not Wnt signaling, what else reprograms a cell to become cartilage?
As a result of investigating this mystery, a second important finding was made: GATA 3, an alternate activity of β-catenin responsible for flipping skeletal cell destiny. Cartilage-specific gene expression is activated in cells by a single gene regulator called GATA3. According to Dr. Wei Hsu, GATA3 interacts to the genomic sequences essential for the reprogramming. Like utilizing four stem cell factors to make embryonic stem cell–like cells termed induced pluripotent stem cells (iPSC), GATA3 is a major changer since it may be used to convert any somatic cell into a cartilage–forming cell.
This has huge implications for the development of novel therapies for the 1 in 4 individuals who are living with cartilage injuries and cartilage degeneration since it allows a cell to be directed to become bone, cartilage, or fat. Current therapies are unable to enhance joint function, and a cure for cartilage regeneration remains uncertain.
This study is a major advancement in the field of tissue regeneration research and has great promise for providing significant comfort to thousands of sufferers.
Takamitsu Maruyama, Daigaku Hasegawa, Tomas Valenta, Jody Haigh, Maxime Bouchard, Konrad Basler, Wei Hsu. GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis. Science Advances, 2022; 8 (48) DOI: 10.1126/sciadv.add6172
Forsyth Institute. (2022, November 30). Scientists discover a new mechanism to generate cartilage cells. ScienceDaily. Retrieved December 3, 2022 from www.sciencedaily.com/releases/2022/11/221130151516.htm