Journal article
Comparison of cellular responses to TGF-β1 and BMP-2 between healthy and torn tendons
- Abstract:
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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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(Preview, Version of record, pdf, 2.1MB, Terms of use)
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- Publisher copy:
- 10.1177/03635465211011158
Authors
- 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:
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1552-3365
- ISSN:
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0363-5465
- Pmid:
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34081556
- Language:
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English
- Keywords:
- Pubs id:
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1181910
- Local pid:
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pubs:1181910
- Deposit date:
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2023-01-20
- ARK identifier:
Terms of use
- Copyright holder:
- Morita et al.
- Copyright date:
- 2021
- Rights statement:
- © 2021 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 License which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages.
- Licence:
- CC Attribution (CC BY)
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