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Dexamethasone treatment influences tendon healing through altered resolution and a direct effect on tendon cells.

Published version
Peer-reviewed

Repository DOI


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Authors

Dietrich-Zagonel, Franciele 
Alim, Md Abdul 
Beckman, Leo Bon 

Abstract

Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells. Rats (n = 36) were randomized to heavy loading or mild loading, the Achilles tendon was transected, and animals were treated with dexamethasone or saline. Gene and protein analyses of the healing tendon were performed for extracellular matrix-, inflammation-, and tendon cell markers. We further tested specific effects of dexamethasone on tendon cells in vitro. Dexamethasone increased mRNA levels of S100A4 and decreased levels of ACTA2/α-SMA, irrespective of load level. Heavy loading + dexamethasone reduced mRNA levels of FN1 and TenC (p < 0.05), while resolution-related genes were unaltered (p > 0.05). In contrast, mild loading + dexamethasone increased mRNA levels of resolution-related genes ANXA1, MRC1, PDPN, and PTGES (p < 0.03). Altered protein levels were confirmed in tendons with mild loading. Dexamethasone treatment in vitro prevented tendon construct formation, increased mRNA levels of S100A4 and decreased levels of SCX and collagens. Dexamethasone during tendon healing appears to act through immunomodulation by promoting resolution, but also through an effect on tendon cells.

Description

Funder: Linköping University

Keywords

Achilles tendon, Corticosteroids, In vitro, Injury, Loading, Resolution, Dexamethasone, Animals, Rats, Wound Healing, Tendon Injuries, Achilles Tendon, S100 Calcium-Binding Protein A4, Male, Annexin A1, Actins, Collagen, Rats, Sprague-Dawley, Tendons, Extracellular Matrix, RNA, Messenger, Basic Helix-Loop-Helix Transcription Factors

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
Stiftelsen Lars Hiertas Minne (FO2020-0178)
Vetenskapsrådet (VR2017-00990)
Åke Wiberg Stiftelse (M20-0021)
Magnus Bergvalls Stiftelse (2019-03211)
Centrum för idrottsforskning (2022-0094)