# Inflammation in Rotator Cuff Tear and Repair

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $164,053

## Abstract

This NIAMS K08 Proposal seeks to provide a clinician-scientist career development opportunity for a promising
junior orthopaedic shoulder surgeon with clinical expertise in reconstructive shoulder surgeries. The candidate
had research training in shoulder animal experiments during medical school education and residency. The
Mentoring and Research Support Committee is ready to provide rigorous guidance for learning multi-
disciplinary mechanistic research knowledge and skills that will be most critical for the candidate's
development into an independent orthopaedic surgeon scientist. The candidate has strong institutional support
with protected research time. Rotator cuff disorders are some of the most common musculoskeletal disorders,
yet treatments need further improvement. Scientific discoveries about rotator cuff disorders can be applied to
other inflammatory, degenerative, or traumatic disorders in different anatomic locations. Our research project
was deliberately chosen to provide training opportunities that will lead to clinically impactful discoveries,
thereby fulfilling all necessary elements of the most successful K08 Award requirements. The shoulder joint is
the most mobile joint in the human body, steered by a rotator cuff consisting of tendons arising from the
scapula and inserting in a tight region on the top end of the humerus. As a result, the rotator cuff is vulnerable
to wear-and-tear of the tendons and inflammation of the bursa, resulting in shoulder pain and dysfunction. Our
long-range scientific goal is to establish a molecular therapeutic approach for the treatment of rotator cuff
disorders. We can then apply this therapeutic approach to treat other inflammatory disorders in the
musculoskeletal system. Our Preliminary Data showed that inflamed human rotator cuff tissues and cells
express higher levels of cytokines and chemokines compared to normal rotator cuff tissues. One of the most
striking inflammatory mediators is stromal cell derived factor-1 (SDF-1), which is a chemokine responsible for
mobilizing inflammatory cells bearing CXCR4/7, a specific receptor for SDF-1. We have established rat rotator
cuff tear models that simulate human rotator cuff inflammation. Our central hypothesis is that SDF-1/CXCR4/7
targeting mitigates rotator cuff inflammation and promotes healing of the tendon repair around the shoulder
joint. We will conduct rigorous scientific experiments to accomplish the following two Specific Aims. (1) To
determine whether SDF-1/CXCR4/7 mediates recruitment of inflammatory cells, cytokine expression, and
M1/M2 macrophage polarization at the site of tendon-bursal cell interactions in vitro. (2) To determine whether
SDF-1/CXCR4/7 targeting reduces inflammation and enhances repair of torn rotator cuff tendons in vivo. Our
proposal is impactful in the era of Precision Medicine because we are introducing a new therapeutic paradigm
for shoulder disorders by targeting SDF-1 or other key mediators of inflammation wit...

## Key facts

- **NIH application ID:** 10102204
- **Project number:** 5K08AR072092-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** David Kovacevic
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,053
- **Award type:** 5
- **Project period:** 2019-01-15 → 2021-02-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102204

## Citation

> US National Institutes of Health, RePORTER application 10102204, Inflammation in Rotator Cuff Tear and Repair (5K08AR072092-05). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10102204. Licensed CC0.

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