The Columbia College of Dental Medicine has identified stem cells in the temporomandibular joint (TMJ) that can make new cartilage and repair damaged joints. When these stem cells were manipulated in animals with TMJ degeneration, the repaired cartilage in the joint. A single cell transplanted in a mouse spontaneously generated cartilage and bone and even began to form a bone marrow niche.
“This is very exciting for the field because patients who have problems with their jaws and TMJs are very limited in terms of clinical treatments available,” said Mildred C. Embree, DMD, PhD, assistant professor of dental medicine at the Columbia University Medical Center (CUMC) and lead author of the study.
Up to 10 million people in the United States, primarily women, have TMJ disorders, according to the National Institutes of Health. Current treatment options include surgery or palliative care, which addresses symptoms but can’t regenerate the damaged tissue. However, these findings suggest that stem cells already present in the joint could be manipulated to repair it.
Fibrocartilage, the type of cartilage in the TMJ, also is found in the knee meniscus and in the discs between the vertebrae. It cannot regrow or heal, so disease and injuries that damage it can lead to permanent disability. Researchers have been investigating the use of the patient’s own stem cells to regenerate this cartilage due to the challenges of transplanting donor stem cells, which include the possibility of rejection by the recipient.
“The implications of these findings are broad, including for clinical therapies. They suggest that molecular signals that govern stem cells may have therapeutic applications for cartilage and bone regeneration,” said Jeremy Mao, DDS, PhD, the Edwin S. Robinson professor of dentistry in orthopedic surgery at CUMC and co-director of the Center for Craniofacial Regeneration at Columbia. “Cartilage and certain bone defects are notoriously difficult to heal.”
The researchers isolated fibrocartilage stem cells (FCSCs) from the joint and showed that they can form cartilage and bone, both in the laboratory and when implanted into animals. They did not have to add any reagents to the cells, since they already were programmed to form bone and cartilage. And while some approaches to regenerating injured tissue require growth factors or biomaterials for cells to grow on, the FCSCs grew and matured spontaneously.
Also, the researchers identified a molecular signal, Wnt, that depletes FCSCs and causes cartilage degeneration. Injecting a Wnt-blocking molecule called sclerostin into degenerated TMJs in animals stimulated cartilage growth and joint healing. Now, the researchers are looking for other small molecules that could be used to inhibit Wnt and promote FCSC growth. The goal will be to find a drug with minimal side effects that could be injected right into the joint.
For example, children with juvenile idiopathic arthritis can have stunted jaw growth that can’t be treated with existing drugs, Embree noted. Since the TMJ is a growth center for the jaw, the research may offer strategies for treating these children and lead to a better understanding of how the jaw grows and develops. While orthodontists now use headgear to modify jaw growth, these findings could point toward growth modulation on the cellular level. They also could lead to strategies for repairing cartilage elsewhere, like the knees and vertebral discs.
“Those types of cartilage have different cellular constituents, so we would have to really investigate the molecular underpinnings regarding how these cells are regulated,” Embree said.
The study, “Exploiting Endogenous Fibrocartilage Stem Cells to Regenerate Cartilage and Repair Joint Injury,” was published by Nature Communications.
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