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Mapping temporomandibular joint (TMJ) degeneration and pain

Award Number: R01DE033511
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Mapping temporomandibular joint (TMJ) degeneration and pain - PROJECT SUMMARY/ABSTRACT Temporomandibular joint (TMJ) osteoarthritis (TMJOA) is a degenerative disease of the joint. It has been challenging to manage and treat TMJOA due to our limited understanding of the molecular, cellular, and neuronal mechanisms underlying TMJOA. The goal of this proposal is to use multi-modal single-cell and imaging technologies to establish a high-dimensional, comprehensive molecular, cellular, and innervation map of TMJ under healthy and OA conditions in mouse models that mimic human TMJOA. We will further validate Netrin- 1/Dcc as the potential therapeutic target of TMJOA. A major strength of this collaborative project is to integrate the findings, skills, and distinct expertise of investigators including PI Jianfu Chen (Neuroscience), co-Is Mildred Embree and Yang Chai (Craniofacial biology and TMJOA), collaborator Xu Cao (Neuroskeletal pain) and Hu Zhao (TESOS volume imaging), which cannot otherwise be accomplished by the individual investigators separately. Strong published and preliminary studies support comprehensive team of scientific approaches in unveiling the mechanisms of TMJOA, including different TMJOA mouse models, methodology for joint pain behavior, dynamic changes in joint pathologies and innervation during OA, 3-D imaging methods to map sensory nerve connectome in the TMJ at micron resolution, antegrade and retrograde tracing of joint innervation, chemogenetic functional assays of neural circuits, and single cell RNA-sequencing approaches. Importantly, our preliminary studies have identified Netrin-1/Dcc as key mediators of TMJ cell-cell interaction and potential therapeutic targets for mitigating TMJOA pain. These exciting preliminary data put us in a unique position to generate the first comprehensive molecular, cellular, and innervation map of TMJ with or without OA and to identify new therapeutic targets. Our guiding hypothesis is that TMJOA causes significant alterations in chromatin accessibility and gene expression of disease relevant cell types including osteoclasts and synovial fibroblasts in TMJ, which in turn cause maladaptive nociceptive innervation leading to joint pain and degeneration. To test our hypothesis, we will: (1) create a comprehensive single-cell transcriptomic and epigenomic cell atlas for the TMJ in TMJOA model mice and identify molecular changes that accompany TMJOA in each cell type. (2) functionally map TMJ nociceptive innervation during OA progression. (3) validate Netrin-1/Dcc as mediators and therapeutic targets of TMJOA pain.


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: 2026 ( Subtotal = $561,693 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	5/5/2026	NON-COMPETING CONTINUATION	$561,693
														Subtotal = $561,693

Issue Date FY: 2025 ( Subtotal = $571,329 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	2	5/9/2025	NON-COMPETING CONTINUATION	$57,134
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	4/22/2025	NON-COMPETING CONTINUATION	$514,195
														Subtotal = $571,329

Issue Date FY: 2024 ( Subtotal = $589,725 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	6/28/2024	NEW	$589,725
														Subtotal = $589,725

Grand Total All Awards = $1,722,747

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Mapping temporomandibular joint (TMJ) degeneration and pain

Award Number: R01DE033511

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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