# The role of mitochondrial Damage Associated Molecular Patterns (mDAMPs) in posttraumatic osteoarthritis.

> **NIH NIH R03** · CORNELL UNIVERSITY · 2020 · $78,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 This application seeks funding to support a NIAMS K08 recipient during her transition to research
independence. The broad objective is to investigate the role of mitochondrial Damage-Associated Molecular
Patterns (mDAMPs) after cartilage injury and in the development of posttraumatic osteoarthritis (PTOA).
 In many tissues, injury-induced mitochondrial dysfunction causes cells to release mDAMPs into the
extracellular environment, which perpetuates inflammation and leads to ongoing tissue damage. Recent work,
performed during the applicant’s K08 award, demonstrated that mitochondrial dysfunction is an acute response
of chondrocytes to cartilage injury, and importantly, mitoprotective therapy prevents cell death and cartilage
degeneration. However, the basic mechanisms whereby mitochondrial dysfunction leads to PTOA are not well
understood, and mDAMPs have not been studied in cartilage. To test the hypothesis that mDAMPs are released
from chondrocytes undergoing injury-induced mitochondrial dysfunction, and that these damage signals are
associated with clinical joint trauma, we will measure mDAMPs in four different model systems.
 The goal of Aim 1 is to identify specific signals that initiate mDAMP release. First, chondrocytes will be
stressed in vitro using several stimuli known to induce mDAMP release in other cell types. Inhibitors of
mitochondrial dysfunction and mitophagy will also be tested for their ability to block mDAMP release. Next, we
will determine if mechanical injury to cartilage explants results in mDAMP release ex vivo. The results of Aim 1
will provide insight into how mDAMP release is triggered, and how it may be manipulated therapeutically.
 Aim 2 will analyze mDAMPs in equine synovial fluid to determine if articular injury results in mDAMP release
in vivo. mDAMP concentration will be measured in banked synovial fluid from previous studies, where horses
had experimental joint injury, with and without intraarticular mitoprotective therapy. To determine if mDAMP
release is associated with naturally occurring disease, mDAMPs will be measured in equine synovial fluid from
clinical patients with acute joint trauma. Results of Aim 2 will determine if mitoprotection can prevent mDAMP
release in vivo, and if synovial fluid mDAMPs are useful indicators of early cartilage/bone injury.
 This proposal builds on the applicant’s K08 research, and utilizes samples generated during those studies,
allowing the proposed aims to be accomplish within the 2-year time frame. These studies represent a new line
of inquiry, independent from the applicant’s mentor. Dr. Delco solely generated the research concept, designed
the experiments, wrote the proposal, and will be responsible for project oversight. By establishing a new area of
research within the field, this award will allow Dr. Delco to build an independent research program and continue
to develop a niche in mitochondrial biology in osteoarthritis and regenerative medic...

## Key facts

- **NIH application ID:** 9974472
- **Project number:** 5R03AR075929-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Michelle Lee Delco
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,500
- **Award type:** 5
- **Project period:** 2019-07-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974472

## Citation

> US National Institutes of Health, RePORTER application 9974472, The role of mitochondrial Damage Associated Molecular Patterns (mDAMPs) in posttraumatic osteoarthritis. (5R03AR075929-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9974472. Licensed CC0.

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