# CMA: Cartilage Repair Strategies to Alleviate Arthritic Pain (CaRe AP): Optimizing the Host Environment for Intra-articular Osteoarthritis Therapies

> **NIH VA I01** · OKLAHOMA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

Osteoarthritis (OA) is highly prevalent in U.S. military service members and Veterans due to the impact of joint
trauma and overuse injury. Its socioeconomic impact is substantial, estimated to approach $60 billion per year,
and no disease-modifying treatments exist. The overall goal of the collaborative Program is to develop a
treatment for post-traumatic osteoarthritis (PTOA) that will relieve pain and improve function. We hypothesize
that PTOA is caused by maladaptive repair responses including activation of the pro-inflammatory pathways of
innate immunity that in turn result in pain, loss of function and structural decline. This Program address the
hypothesis through two highly-integrated aims: (1) developing innovative non-pharmacologic and intra-articular
therapies inhibiting local pain and inflammation, and (2) optimizing mesenchymal stem cell (MSC)-based
therapies for reconstruction of the damaged joint. The goal of Project 5 is to identify pragmatic evidence-based
interventions that reduce PTOA pain and increase the efficacy of intra-articular therapies using a pre-clinical
animal model of Veteran-specific health conditions. A major barrier to progress in the field is developing
therapeutic approaches that resolve chronic PTOA inflammation and stop the structural progression of disease.
It is likely that combined therapeutic approaches will be required to overcome this barrier and develop safe and
effective treatments for Veterans. Our proposed studies will address this unmet need by determining how mild
exercise therapy and intra-articular corticosteroid treatments (IA-CST) function independently and in
combination to alter molecular and structural conditions of the intra-articular "host environment" that reduce
pain and improve the efficacy of cell-based PTOA therapies. The rationale for this project is that identifying
non-surgical interventions that increase the efficacy and pain relief of disease modifying OA therapies will
greatly improve their cost-effectiveness and the path toward clinical implementation. We hypothesize that mild
exercise therapy will improve the efficacy of intra-articular OA therapies by reducing joint inflammation,
reversing the pro-catabolic effects of IA-CST, and rescuing epigenetic changes that negatively impact
autologous and allogenic stem cell therapies. A key aspect of our approach to testing this hypothesis is to use
older (6-12 months old) high-fat diet-induced obese mice. These mice share many clinical features with the
Veteran population most in need of OA therapies who are older, obese, and afflicted with metabolic syndrome-
related comorbidities. This project capitalizes on our expertise in the use of this pre-clinical animal model to
study OA pathophysiology. We will use the destabilized medial meniscus model of PTOA in these mice to
complete three specific aims. For each aim, we will determine the independent and combined effects of intra-
articular CST (triamcinolone acetonide) and mild treadmi...

## Key facts

- **NIH application ID:** 10111342
- **Project number:** 5I01BX004882-02
- **Recipient organization:** OKLAHOMA CITY VA MEDICAL CENTER
- **Principal Investigator:** TIMOTHY M GRIFFIN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111342

## Citation

> US National Institutes of Health, RePORTER application 10111342, CMA: Cartilage Repair Strategies to Alleviate Arthritic Pain (CaRe AP): Optimizing the Host Environment for Intra-articular Osteoarthritis Therapies (5I01BX004882-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10111342. Licensed CC0.

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