# Imaging and therapeutic targeting of tissue crosstalk in the injured knee

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $742,834

## Abstract

The inability to slow or revert progression to posttraumatic osteoarthritis (PTOA) after injury has devastating
consequences for a young population, whose only therapeutic option remains knee replacement at a young age.
Despite extensive research, PTOA pathophysiology continues to be poorly understood which translates in
suboptimal diagnosis tools and limited treatment options. Although there is consensus that cell death (apoptosis)
and low-grade inflammation play a major role in PTOA onset, we lack understanding on how these factors tip
the healing response to injury into a vicious cycle of perpetuating joint damage. Unfortunately, blocking
inflammation or apoptosis alone has proven to be insufficient to prevent progression to PTOA. In our preliminary
studies we found a synergistic interaction between apoptotic articular chondrocytes and the inflammatory
response of synovial cells that exacerbates apoptosis and inflammation creating a devastating production of pro-
inflammatory and catabolic signaling. Thus, we hypothesize that a combinatorial treatment targeting apoptosis
and inflammation is needed to reinstate joint homeostasis after injury. Here we propose a comprehensive
approach to characterize the crosstalk between inflammation and apoptosis in vitro and in vivo. We will identify
in vitro the crosstalk mechanisms and the molecular interplay between apoptosis and inflammation by analyzing
the transcriptome of articular chondrocytes and synovial cells exposed to one or both stimuli and by
characterizing the paracrine signaling. In vitro studies will allow us to study single interactions between cells and
stimuli. We will then assess inflammation and apoptosis in vivo. Studying the dynamic crosstalk between events
in knee joints represents a major challenge since we need to capture two processes in the same animal in vivo
overtime. Molecular imaging represents a natural approach that can capture both inflammation and apoptosis in
the same animal overtime and make possible the study of the dynamic synergistic interaction between these two
processes. We will combine our novel MRI contrast agent that detects pro-inflammatory signaling in articular
cartilage, with optical imaging agents targeting apoptosis and a positron emission tomography (PET) tracer
targeting the folate receptor expressed in activated macrophages. This multimodal imaging approach will allow
longitudinal assessment of the activity and timing of inflammation and apoptosis during the progression to PTOA.
We will investigate in vivo the effect of blocking apoptosis has in inflammation and vice versa. Finally, a
combinatorial treatment targeting apoptosis and inflammation will be explored to reinstate joint homeostasis after
injury. These studies will lay the groundwork for the development of therapeutic strategies targeting the crosstalk
between apoptosis and inflammation but also contribute to a fundamental understanding of how the interplay of
crucial pathological mechanism can...

## Key facts

- **NIH application ID:** 10803635
- **Project number:** 1R01AR082670-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Maria Amparo Ruiz Garzon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $742,834
- **Award type:** 1
- **Project period:** 2024-03-15 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803635

## Citation

> US National Institutes of Health, RePORTER application 10803635, Imaging and therapeutic targeting of tissue crosstalk in the injured knee (1R01AR082670-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803635. Licensed CC0.

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