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

Award Number: R01DE021134
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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 morphology results in subject-specific differences in temporomandibular biomechanics, and identification of TMDD-specific mechanobiological bio-indicators.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $462,321 )
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	9	1/16/2024	NON-COMPETING CONTINUATION	$424,580
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	001	9	6/14/2024	NON-COMPETING CONTINUATION	$37,741
														Subtotal = $462,321

Issue Date FY: 2023 ( Subtotal = $471,755 )
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	002	8	3/9/2023	NON-COMPETING CONTINUATION	$47,175
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	001	8	2/13/2023	NON-COMPETING CONTINUATION	$0
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	8	1/31/2023	NON-COMPETING CONTINUATION	$424,580
														Subtotal = $471,755

Issue Date FY: 2022 ( Subtotal = $467,038 )
2022	2022	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	002	7	4/20/2022	NON-COMPETING CONTINUATION	$42,459
2022	2022	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	001	7	2/2/2022	NON-COMPETING CONTINUATION	$424,579
2022	2021	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	6	1/19/2022	COMPETING CONTINUATION	$0
														Subtotal = $467,038

Issue Date FY: 2021 ( Subtotal = $484,880 )
2021	2021	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	6	1/27/2021	COMPETING CONTINUATION	$484,880
														Subtotal = $484,880

Issue Date FY: 2020 ( Subtotal = -$893 )
2020	2016	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	5	1/10/2020	EXTENSION WITH OR WITHOUT FUNDS	-$893
														Subtotal = -$893

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2016	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	5	3/6/2019	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	5	2/23/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $371,525 )
2016	2016	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	5	3/1/2016	EXTENSION WITH OR WITHOUT FUNDS	$371,525
														Subtotal = $371,525

Issue Date FY: 2015 ( Subtotal = $500,230 )
2015	2015	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	4	2/25/2015	NON-COMPETING CONTINUATION	$500,230
														Subtotal = $500,230

Issue Date FY: 2014 ( Subtotal = $533,897 )
2014	2014	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	3	2/10/2014	NON-COMPETING CONTINUATION	$480,507
2014	2014	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	001	3	2/28/2014	NON-COMPETING CONTINUATION	$53,390
														Subtotal = $533,897

Issue Date FY: 2013 ( Subtotal = $531,230 )
2013	2013	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	002	2	9/23/2013	SUPPLEMENT FOR EXPANSION	$174,976
2013	2013	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	2	2/8/2013	NON-COMPETING CONTINUATION	$333,989
2013	2013	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	001	2	5/9/2013	NON-COMPETING CONTINUATION	$22,265
														Subtotal = $531,230

Issue Date FY: 2012 ( Subtotal = $394,925 )
2012	2012	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Oral Diseases and Disorders Research	000	1	3/6/2012	NEW	$394,925
														Subtotal = $394,925

Grand Total All Awards = $4,216,908

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

Award Number: R01DE021134

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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