# Integrating craniofacial morphology, oral function, temporomandibular biomechanics and mechanobiology to determine sex-specific TMJ pathophysiology in humans

> **NIH NIH R01** · CLEMSON UNIVERSITY · 2024 · $462,321

## Abstract

Project Summary
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 mo...

## Key facts

- **NIH application ID:** 10773056
- **Project number:** 5R01DE021134-09
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Hai Yao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,321
- **Award type:** 5
- **Project period:** 2012-03-06 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773056

## Citation

> US National Institutes of Health, RePORTER application 10773056, Integrating craniofacial morphology, oral function, temporomandibular biomechanics and mechanobiology to determine sex-specific TMJ pathophysiology in humans (5R01DE021134-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10773056. Licensed CC0.

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