Researchers Receive Grant to Study TMJ Biology, Long-term Maintenance

Of all the joints in the body, perhaps the most unique, complex, and understudied is the temporomandibular joint (TMJ). The TMJ, which is located close to the ears, is a bilateral movable articulation, connecting the lower jaw (mandible) to the bone at the side of the skull (temporal bone). Its structure include a distinctive feature called an articular disc that acts as a shock absorber and reduces friction so that the bony parts of the joint can glide smoothly, allowing us to chew, talk, yawn, and open our mouths wide to say “Ahhh.”

Researchers at The Children’s Hospital of Philadelphia, Eiki Koyama, DDS, PhD, a faculty member in the Division of Orthopedics, and Hyun-Duck Nah, DMD, PhD, an orthodontist in the Division of Plastic and Reconstructive Surgery who works with patients who have craniofacial deformities, recently received a grant from the National Institute of Dental & Craniofacial Research to study the development of the TMJ, the mechanisms that maintain it, and how these processes may be altered in disease. They aim to use this knowledge to inform future therapeutic strategies in pediatric and adult medicine.

The TMJ begins to form within the first few months after conception, experiences active growth during childhood and adolescence, and then undergoes adaptive remodeling throughout life. The exact prevalence of TMJ disorders in the general pediatric population is uncertain, but guidelines from the American Academy of Pediatric Dentistry cite that upwards of 25 percent of children ages 5 to 17 have some symptoms of TMJ disease, and 1 percent to 2 percent are in need of treatment.

Pediatric TMJ disorders can be congenital or acquired, such as craniofacial abnormalities, juvenile rheumatoid arthritis, and injuries or infection that damage the joint. Symptoms and signs of TMJ disorders vary depending on etiology and severity, but commonly include difficulty opening the mouth, locking of the joint, difficulty with mastication and nutrition, and facial and jaw muscle pain. Furthermore, defective TMJ function often results in under-development of the mandible and abnormal facial growth.

In previous research, Dr. Koyama’s group demonstrated that mice with deletion of a specific gene, Indian hedgehog (Ihh), failed to form a normal TMJ. The joint lacked integral components including its distinctive articular disc, joint cavities, and the specialized cell layers that produce lubricin. Lubricin is a lubricant that protects the TMJ from frictional loads and thus is essential for long-term maintenance of joint integrity.

In the current study, the Koyama and Nah team now plan to further define the roles of Ihh and additionally to delineate the role of two genetic pathways, TGF-β1 and PTHrP, that they suggest Ihh uses to orchestrate TMJ formation, function, and lubricin production. They predict that deterioration of joint lubrication with age or by other insults may underlie disc adhesion and degenerative TMJ disorders, which are prevalent in the adult population.

While this research is still at the basic science stage, Dr. Nah, who is also a research associate professor of surgery at the Perelman School of Medicine at the University of Pennsylvania, said that the ultimate goals of the study include translation of findings to recreate a functional TMJ for those patients with missing or defective TMJs.