Since early days, TMJA has advocated for research to advance understanding of the TM joint, the most complex joint in the body, urging the National Institutes of Health (NIH) to put more effort into studies of basic anatomy and physiology, and of genetics and risk factors. We are pleased to report that TM joint research is underway and is benefiting from more sophisticated tools and technology. Herewith are some examples of research currently supported by NIH. Note that the grants describe the aims of research rather than new findings.
Alejandro Almarza, Ph.D. at the McGowan Institute of Regenerative Medicine at the University of Pittsburgh is working to develop a replacement for the TM disc using biologic extracellular matrix material (ECM) tissue. “Extracellular matrix” consists of materials and molecules in the ground substance surrounding various cells and organs in the body. The EMC implant Dr. Almarza is using consists of a powdered form of ECM sandwiched between layers of the same material. The ECM, derived from pig bladders, is shaped to model the TMJ disc and implanted into animal models. Dr. Almarza hopes this research will serve as a template for the formation of new, site-appropriate, functional TMJ disc tissue.
Kyriacos Athanasiou, Ph.D., P.E. at the University of California, Davis, and a member of TMJA’s Scientific Board, has two grants directed toward developing tissueengineered replacements for various components of the TM joint. One grant is using co-cultures of fibrocartilage and cartilage cells to mimic the dimensions and make-up of the cartilage surface of the mandible and of the joint disc. By supplying various growth factors in the cell culture medium along with mechanical stimulation, Dr. Athanasiou hopes to enhance the mechanical properties of the constructs enabling them to function as well as healthy native tissue under the various demands of joint function. The constructs will be implanted and tested in an immunodeficient mouse model. A second grant is directed to implanting an anatomically correct and robust TMJ disc, with attachments, to replace a disc with commonly seen disc pathology, including perforations and damage in the lateral regions.
Yiping Chen, Ph.D. at Tulane University School of Medicine in Louisiana, is looking at the underlying genetic, cellular and molecular mechanisms involved in development of the TMJ that could give rise to congenital jaw ankylosis—a condition of limited mouth opening caused by adhesion of the condyle with joint components in the skull. He has identified a major embryonic developmental gene, Shox2, which, when conditionally inactivated at a stage in development, causes jaw tissue abnormalities and ankylosis. The aims of his research will be to use a mouse model to determine the genes regulated by Shox2, explore how the Shox2 gene itself can be modulated and compare the mouse gene to its human counterpart.
Sunil Kapila, B.D.S., M.S., Ph.D. at the University of Michigan Dental School, is studying the role of female hormones and their receptors in TMD. Earlier studies indicate that estrogen and/or relaxin contribute to the degeneration of TMJ soft tissues by expression of specific tissue-degrading enzymes called matrix metalloproteinases (MMPs), while progesterone attenuates MMP expression. The new research will explore the dose-response effects of relaxin/progesterone in enhancing/attenuating loss of TMJ disc substance; determine the specific MMPs involved in degradation by using mouse models in which genes coding for specific MMPS are selectively removed (“knocked out”) and, similarly, use mice in which specific estrogen and relaxin receptor genes have been knocked out, to identify which hormone receptors contribute to joint degradation.
Jeffrey Nickel, D.M.D., M.Sc., Ph.D. at the University of Missouri-Kansas City is studying mechanical fatigue failure of TMJ tissues, which could cause disc dysfunction, inflammation, pain and bony changes. Mechanical fatigue depends on the magnitude of energies exerted on the jaws and the extent of load bearing. His initial findings suggest that higher energy densities occur in women compared to men, and in individuals with disc displacement compared to a healthy group. His grant will follow up on initial findings and use jaw imaging, and energy and load-bearing measurements, to compare men and women, and subjects with and without disc displacement and/or joint pain. He will factor in genetic analyses to determine if having gene variants that increase sensitivity to pain, along with higher energy density and jaw loading, can predict disc position in subjects with and without joint pain.
Patricia Purcell, Ph.D. at Children’s Hospital Boston/Harvard Medical School, is looking at the molecular and cellular mechanisms of TM joint formation. Dr. Purcell believes that using a technique called laser capture microdissection that isolates different parts of the TM joint in mouse embryonic tissue, will reveal which genes are present in each location, with the final goal of establishing a “blueprint” of the TM joint. She believes this research may provide new “biomarkers” that are increased or decreased in TMJ Disorders, and could be used to predict the risk that an individual will develop TMJ Disorders. Furthermore, the molecular information gained from this research may assist in the devising of alternative therapeutic approaches for TM Joint Disorders, as well as ultimately in bioengineering replacements for defective or damaged TM joint structures.
Gordana Vunjak-Novakovic, Ph.D. at Columbia University is using stem cells to grow grafts of bone in the shape of the TM joint using a bioreactor and is able to control the factors that enter the bioreactor over time. These factors include essential nutrients, oxygen, and physical factors that keep these large pieces of bone alive and functional. Dr. Vunjak-Novakovic believes this research will someday help patients who have had TMJ implants or may be contemplating implant surgery down the road. The bioengineered bone grafts are currently being tested in an animal model, but the commercial technology is only a few years away.
Hai Yao, Ph.D. at the Medical University of South Carolina explains that the TMJ disc is a large soft tissue structure without blood vessels and dependent on a nutrient supply for its maintenance and health. Using a pig model, he aims to develop a non-invasive “integrated dynamic measuring system” to establish quantitative relationships between jaw mechanical loading (pattern and magnitude), nutrient concentration profiles (oxygen, glucose, lactate), and metabolic rates in the disc. He believes that nutrient concentration and metabolic rates are sensitive to jaw loading during jaw function and thus could be early bio-indicators for evaluating the effects of mechanical loading on temporomandibular disorders.