Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis
NIDCR - National Institute of Dental and Craniofacial Research
About This Grant
The Temporomandibular Joint (TMJ) is the most-used joint in the body. The TMJ cartilage carries out the essential function of enabling free joint movement during speech and mastication. TMJ Osteoarthritis (TMJ-OA) consist of osteochondral tissue degeneration and is a growing epidemic that afflicts men and women not only in United States but across the globe. It is well established that altered expression and activation of catabolic enzymes underlies joint cartilage destruction observed in TMJ-OA, however the precise mandibular chondrocyte behavior during TMJ cartilage degeneration and regeneration is not well understood. Notch signaling has been identified as a potential catabolic and anabolic mediator of TMJ-OA. Understanding Notch cellular signaling that regulate osteochondral tissue degeneration can lead us to development of new therapeutic targets. To sufficiently advance our understanding of Notch signaling in TMJ degeneration-regeneration and translate our findings, will require robust experimentation, including preclinical studies in TMJ degeneration model. Our long-term goal is to develop a clinically relevant approach to modulate Notch signaling to prevent TMJ degeneration and facilitate its regeneration. Our central hypothesis is that Notch ligand (Jagged 1 / 2) is a potential target for TMJ- OA, and they work via upregulation of bone morphogenetic protein 2 (BMP2) and Indian hedgehog (Ihh) signaling pathway. This work will be completed in three specific aims, using novel mouse model and state of art genomic technology. Our preliminary work has demonstrated that Jagged 1 is significantly over expressed (both mRNA & protein) in TMJ degeneration both in mice and humans. In specific aim 1, we will disrupt Jagged1/2 in lineage specific manner in chondrocytes and osteoblasts of subchondral bone. In specific aim 2, we will define the pathophysiological mechanism by which Notch ligand (Jagged 1 / 2) leads to TMJ degeneration and regeneration at single cell level and in specific aim 3, our experiments will translate our mechanistic observation and study the role Jagged1/2 plays in traumatic TMJ injury and repair, specifically using anti-Jagged 1 antibodies to reduce TMJ degeneration. The proposed project has immense potential to reveal new regulatory pathways that modulates TMJ degeneration and regeneration and to open new insights on understanding the disease mechanism and developing therapeutic interventions.
Grant Summary
Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis is a NIDCR - National Institute of Dental and Craniofacial Research grant providing up to $414K for university, nonprofit, healthcare org. Applications are due 2030-05-31 (open). Check eligibility and apply with FindGrants.
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Up to $414K
2030-05-31
- 1Confirm your organization is eligible for Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis from NIDCR - National Institute of Dental and Craniofacial Research, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
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Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis: Frequently Asked Questions
Who is eligible for the Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis?
Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis is offered by NIDCR - National Institute of Dental and Craniofacial Research and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis provide?
Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis provides up to $414K per award from NIDCR - National Institute of Dental and Craniofacial Research. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis deadline?
Applications for Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis are due 2030-05-31 (open). Because deadlines can change, verify the date with the funder, NIDCR - National Institute of Dental and Craniofacial Research, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis?
To apply for Molecular Mechanism by which Notch Signaling regulates TMJ Osteoarthritis, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDCR - National Institute of Dental and Craniofacial Research.