# Rotator Cuff Degeneration and Repair

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $478,016

## Abstract

ABSTRACT
Chronic degeneration of the rotator cuff leads to tendon tears and poor healing after surgical repair, with failure
rates after repair ranging from 20-94%, depending on the patient population. Repair-site rupture is primarily
due to poor tendon-to-bone healing: high levels of inflammation lead to fibrovascular scar rather than aligned
collagen, and a fibrocartilaginous transition between tendon and bone is not regenerated. Our overall objective
is to determine the drivers of degeneration using mouse models and then to test treatment strategies related to
these mechanisms in a chronic rat rotator cuff repair model. We have identified two critical features of
degeneration and poor healing: inflammation and a lack of fibrocartilage formation. Specifically, there is
dramatic upregulation of the NFκB inflammatory pathway during tendon healing and a requirement for
hedgehog (Hh) signaling in the formation of fibrocartilage between tendon and bone. Therefore, the current
proposal focuses on these two pathways for preventing degeneration and enhancing healing. Specific Aim 1
seeks to determine the role of inflammation, and the NFκB pathway in particular, in rotator cuff degeneration
and healing. Inflammation will be modulated genetically in mouse models via the activation and deletion of
IKKB, a factor required for NFκB signaling. IKKB will be modulated in tenocytes and muscle cells using
inducible Cre models. To test the therapeutic potential of targeting harmful inflammatory cytokines, an IKKB
inhibitor will be delivered to rats with repaired chronically degenerated rotator cuffs. Specific Aim 2 will
determine role of Hh signaling for fibrocartilage loss during cuff degeneration and fibrocartilage formation
during healing. We will first determine the role of Hh signaling for mineral loss at the healing cuff by deleting
signaling genetically (via tenocyte- or osteoblast-specific inducible Cre models) or increasing signaling with a
Hh agonist. A rat animal model of chronic rotator cuff degeneration followed by repair will then be used to test
the efficacy of a Hh agonist for enhanced tendon-to-bone healing.

## Key facts

- **NIH application ID:** 9987513
- **Project number:** 5R01AR057836-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Leesa M Galatz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $478,016
- **Award type:** 5
- **Project period:** 2010-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987513

## Citation

> US National Institutes of Health, RePORTER application 9987513, Rotator Cuff Degeneration and Repair (5R01AR057836-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987513. Licensed CC0.

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