Temporomandibular disorders affect ~35 million people in the US, with 3-8 times more women affected than men. Approximately 30% of temporomandibular disorder patients experience mechanical dysfunction of the articular disc (an avascular tissue) in the temporomandibular joint (TMJ), a load-bearing joint during oral function. However, the etiology of the temporomandibular disc dysfunction/displacement (TMDD) sub-population is poorly understood, including why women are disproportionately affected. Logical TMDD candidate bio-indicators include craniofacial morphology, TMJ biomechanics, disc nutrient availability, and disc metabolism, each of which show varying degrees of sexual dimorphism. These factors interact such that subject-specific craniofacial morphology drives TMJ biomechanics, and biomechanics regulates TMJ disc nutrient availability and cellular metabolism/homeostasis. Study results from the preceding R01 proved that in pigs the avascular TMJ disc nutrient environment is heavily dependent upon mechanical strain-dependent nutrient diffusion, and the nutrient environment has a profound effect on disc cell proliferation and differentiation leading to tissue dysfunction. Therefore, TMJ biomechanical and mechanobiological differences between sexes driven by craniofacial morphology in humans may be critical. Our preliminary data have demonstrated sex-differences in human TMJ loading due to sexual dimorphisms in craniofacial morphology, plus we have identified a TMJ morphologic phenotype that may also explain sex-differences in TMDD occurrence. Therefore, it is now necessary to determine sex differences in the mechanical strain-dependent nutrient transport properties and nutrient level- dependent energy metabolism of the human TMJ disc and investigate the plausible associations of craniofacial morphology and TMJ biomechanics through the mechanobiological pathway on TMDD development and progression. The central hypothesis of the proposed study is that craniofacial morphologic differences between sexes, as well as between healthy controls and TMDD patients, drive the differences of TMJ biomechanics and disc mechanobiology which can be used to predict individuals at greatest risk for TMDD development and progression. The long-term objectives are to understand the mechanobiological etiology of temporomandibular disorders, to identify risk factors specific for TMDD development, and to define TMDD mechanobiological mechanisms of progression. Through the identification of potential morphologic, biomechanical, and biological risk factors for TMDD development and progression, this work has promising clinical translation and lays the foundation for future human studies. Specific outcomes of the proposed study include: determination of the mechanical strain dependency of the temporomandibular disc nutrient environment and its impact on cell viability and energy metabolism in human tissues, an enhanced understanding of how subject-specific morphology results in subject-specific differences in temporomandibular biomechanics, and identification of TMDD-specific mechanobiological bio-indicators.

Public Health Relevance

The proposed experiments utilize critical biomechanical information and approaches to understanding the temporomandibular joint (TMJ) and associated disc, which were determined by our previous study of pig TMJ. It extends that approach into human patients, and combines it with state of the art patient-specific craniofacial morphology combined with oral function biomechanics. This approach will test healthy males and females, in comparison with those who have TMJ dysfunction, to determine why females get TMJ dysfunction and disease 3-8 times more frequently than males.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Vallejo, Yolanda F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Clemson University
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
Zip Code
Wright, Gregory J; Coombs, Matthew C; Wu, Yongren et al. (2018) Electrical Conductivity Method to Determine Sexual Dimorphisms in Human Temporomandibular Disc Fixed Charge Density. Ann Biomed Eng 46:310-317
Cisewski, Sarah E; Wu, Yongren; Damon, Brooke J et al. (2018) Comparison of Oxygen Consumption Rates of Nondegenerate and Degenerate Human Intervertebral Disc Cells. Spine (Phila Pa 1976) 43:E60-E67
Nickel, J C; Iwasaki, L R; Gonzalez, Y M et al. (2018) Mechanobehavior and Ontogenesis of the Temporomandibular Joint. J Dent Res 97:1185-1192
She, Xin; Wei, Feng; Damon, Brooke J et al. (2018) Three-dimensional temporomandibular joint muscle attachment morphometry and its impacts on musculoskeletal modeling. J Biomech 79:119-128
Coombs, M C; Petersen, J M; Wright, G J et al. (2017) Structure-Function Relationships of Temporomandibular Retrodiscal Tissue. J Dent Res 96:647-653
Wu, Y; Cisewski, S E; Wei, F et al. (2017) Fluid pressurization and tractional forces during TMJ disc loading: A biphasic finite element analysis. Orthod Craniofac Res 20 Suppl 1:151-156
Wu, Yongren; Cisewski, Sarah E; Sun, Yi et al. (2017) Quantifying Baseline Fixed Charge Density in Healthy Human Cartilage Endplate: A Two-point Electrical Conductivity Method. Spine (Phila Pa 1976) 42:E1002-E1009
Wei, F; Van Horn, M H; Coombs, M C et al. (2017) A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of women. J Oral Rehabil 44:517-525
Hepfer, R Glenn; Brockbank, Kelvin G M; Chen, Zhen et al. (2016) Comparison and evaluation of biomechanical, electrical, and biological methods for assessment of damage to tissue collagen. Cell Tissue Bank 17:531-9
Wright, Gregory J; Coombs, Matthew C; Hepfer, R Glenn et al. (2016) Tensile biomechanical properties of human temporomandibular joint disc: Effects of direction, region and sex. J Biomech 49:3762-3769

Showing the most recent 10 out of 26 publications