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Comparison of cellular responses to TGF-β1 and BMP-2 between healthy and torn tendons

Abstract:

Background: Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-β) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation.

Purpose: To understand how TGF-β and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons.

Study Design: Controlled laboratory study.

Methods: Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-β1 (10 ng/mL) or BMP-2 (100 ng/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting.

Results: TGF-β1 treatment induced ACAN mRNA expression in both cell types but less in the diseased compared with healthy cells (P < .05). BMP-2 treatment induced BGN mRNA expression in healthy but not diseased cells (P < .01). In the diseased cells, TGF-β1 treatment induced increased ACTA2 mRNA expression (P < .01) and increased small mothers against decapentaplegic (SMAD) signaling (P < .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced ACTA2 mRNA expression in the diseased cells only (P < .05).

Conclusion: Diseased tendon–derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-β1 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells.

Clinical Relevance: Findings from this study suggest that diseased tendon–derived cells respond differently than healthy cells in the presence of TGF-β1 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing.

Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1177/03635465211011158

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Research group:
NIHR Oxford Biomedical Research Centre
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Research group:
NIHR Oxford Biomedical Research Centre
Oxford college:
Keble College
Role:
Author
ORCID:
0000-0002-7052-3793
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Research group:
NIHR Oxford Biomedical Research Centre
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Research group:
NIHR Oxford Biomedical Research Centre
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Research group:
NIHR Oxford Biomedical Research Centre
Role:
Author


Publisher:
SAGE Publications
Journal:
American Journal of Sports Medicine More from this journal
Volume:
49
Issue:
7
Pages:
1892-1903
Publication date:
2021-06-01
Acceptance date:
2021-01-04
DOI:
EISSN:
1552-3365
ISSN:
0363-5465
Pmid:
34081556

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