1. Dexamethasone treatment influences tendon healing through altered resolution and a direct effect on tendon cells.
- Author
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Dietrich-Zagonel F, Alim MA, Beckman LB, and Eliasson P
- Subjects
- Animals, Rats, S100 Calcium-Binding Protein A4 metabolism, S100 Calcium-Binding Protein A4 genetics, Male, Annexin A1 metabolism, Annexin A1 genetics, Actins metabolism, Actins genetics, Collagen metabolism, Rats, Sprague-Dawley, Tendons drug effects, Tendons metabolism, Extracellular Matrix metabolism, Extracellular Matrix drug effects, RNA, Messenger metabolism, RNA, Messenger genetics, Basic Helix-Loop-Helix Transcription Factors, Dexamethasone pharmacology, Wound Healing drug effects, Tendon Injuries drug therapy, Tendon Injuries metabolism, Achilles Tendon drug effects, Achilles Tendon metabolism, Achilles Tendon injuries, Achilles Tendon pathology
- 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., (© 2024. The Author(s).)
- Published
- 2024
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