# Myostatin Alters Muscle Composition as The Result of an ACL Injury

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $421,723

## Abstract

Abstract
Anterior cruciate ligament (ACL) reconstruction surgery results in protracted quadriceps weakness that is
associated with poorer outcomes, altered biomechanics and heightened risk of subsequent injuries. Little
progress has been made in improving quadriceps strength and functional outcomes in the past decade.
Alterations in the cellular and morphological composition of the knee extensor muscles contribute to weakness
following an ACL reconstruction. ACL reconstruction induces expression of myostatin, a negative regulator of
muscle growth, locally within the quadriceps. In addition to mitigating muscle regrowth, myostatin also
promotes connective tissue synthesis through activation of figrogenic cells within muscle. The objective of
this proposal is to determine the time course of deleterious changes to the injured ligament and limb muscle
and identify myostatin as integral in the etiology of protracted muscle weakness in individuals following an ACL
tear. Aim 1 will evaluate the timeframe of myostatin induction within the injured ACL and quadriceps. Aim 2
will determine the deleterious changes within the muscle using a mouse model of ACL injury and the efficacy
of follistatin and a soluble form of the myostatin receptor (activin 2B receptor) to mitigate these maladaptations.
Experiments in aim 3 will determine if the competitive inhibition of myostatin is capable of rescuing ACL injury-
induced skeletal muscle weakness. Finally, aim 4 will define if the acute induction of myostatin signaling
following an ACL injury in human subjects predicts reductions in muscle strength, connective tissue infiltration
and dysregulation of skeletal muscle progenitor cells. The identification of myostatin as a therapeutic target
will establish the basis for further research to mitigate myostatin signaling after ACL and other ligamentous
injuries to improve rehabilitative efforts and patient recovery.

## Key facts

- **NIH application ID:** 10127581
- **Project number:** 5R01AR072061-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Christopher Fry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,723
- **Award type:** 5
- **Project period:** 2018-03-26 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127581

## Citation

> US National Institutes of Health, RePORTER application 10127581, Myostatin Alters Muscle Composition as The Result of an ACL Injury (5R01AR072061-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10127581. Licensed CC0.

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