# Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $486,261

## Abstract

Project Summary/Abstract:
Post-traumatic osteoarthritis (PTOA) affects at least 50% of people who sustain a traumatic joint injury such as
anterior cruciate ligament (ACL) rupture, with symptomatic joint pain typically developing within 1-2 decades
following injury. Modulating joint loading (exercise/walking) or unloading (rest/disuse) in the early phase (<7
days) following injury could be used to decrease inflammation and catabolic processes that initiate PTOA.
However, there is currently no clinical consensus on recommendations for joint loading or unloading during the
early phase, and the effect of post-injury loading/unloading on joint degeneration has never been
mechanistically investigated. The overall goal of this research is to determine how biomechanical interventions
can be utilized following joint injury to affect the initiation and progression of PTOA. The proposed studies will
use a clinically relevant injury model (non-invasive, mechanically-induced ACL rupture in mice) and clinically
relevant post-injury conditions (mechanical unloading of the injured limb, intermittent reloading, surgical
restabilization of the joint) to determine the effect of biomechanical therapies for slowing PTOA progression
after injury. We hypothesize that unloading following injury will reduce inflammation, protease activity, and
mechanical damage in the joint during the early post-injury phase, and that mitigation of these early processes
will change the trajectory of PTOA progression relative to normally loaded joints. We further hypothesize that
muscle and bone atrophy associated with unloading will be ameliorated with intermittent reloading without
leading to joint degeneration, and that surgical restabilization of the knee following one week of unloading will
further reduce long-term joint degeneration, while restabilization following one week of normal loading will not
be as effective for changing the trajectory of PTOA. We will first determine the effect of mechanical unloading
during the early phase on inflammatory and catabolic processes and long-term joint degeneration. Next, we will
determine the effect of intermittent reloading on muscle mass and strength, subchondral bone structure, and
long-term joint degeneration. Finally, we will determine the effect of surgical restabilization of the knee
following normal activity or mechanical unloading during the early phase on long-term joint degeneration.
These studies will determine if unloading and other biomechanical treatments during the early post-injury
phase “pause” PTOA development (i.e., delay but do not prevent long-term joint degeneration), or if they are
able to diminish long-term joint degeneration. These studies will allow us to individually evaluate the effects of
joint unloading, intermittent reloading, and surgical joint restabilization following injury, and will provide
mechanistic insights into biomechanical interventions that will inform subsequent clinical studies, potentially
lead...

## Key facts

- **NIH application ID:** 9896699
- **Project number:** 1R01AR075013-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Blaine A. Christiansen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $486,261
- **Award type:** 1
- **Project period:** 2020-03-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896699

## Citation

> US National Institutes of Health, RePORTER application 9896699, Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading (1R01AR075013-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896699. Licensed CC0.

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