Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.

Abstract

OBJECTIVE:

Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone.

METHODS:

Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-β (2.5 or 5.0 ng/ml) or an inhibitor of the TGF-β receptor (A83.01), recombinant human IL-1β and IL-6. Expression levels of the genes encoding for SP (TAC1) and its preferred receptor (NK1R), IL-1α, IL-1β and IL-6 were determined with quantitative PCR and protein levels of SP were examined by EIA and western blot.

RESULTS:

Exposure of human tendon cells to dexamethasone resulted in a time-dependent reduction of mRNA for SP in both hamstrings and Achilles tenocytes, whereas NK1R was unaffected. The reduction of SP mRNA was dependent on signalling through the glucocorticoid receptor. SP protein was substantially decreased by dexamethasone. Dexamethasone also prevented induction of SP by IL-1β and by cyclic mechanical loading.

CONCLUSION:

This study demonstrates that dexamethasone treatment of human tendon fibroblasts reduces the expression of SP through a glucocorticoid receptor-dependent pathway. Drugs interfering with SP signalling could be a future target in the treatment of tendinopathy.

• Authors: Rouhollah Mousavizadeh, Ludvig Backman, Robert G McCormack, Alex Scott
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 54 Issue 2 Pg. 318-23 (Feb 2015) ISSN: 1462-0332 [Electronic] England
• PMID: 25150176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Glucocorticoids
• Receptors, Neurokinin-1
• Substance P
• Dexamethasone

Topics

• Achilles Tendon (metabolism)
• Adult
• Cells, Cultured
• Dexamethasone (pharmacology)
• Down-Regulation
• Female
• Fibroblasts (metabolism)
• Gene Expression
• Glucocorticoids (pharmacology)
• Healthy Volunteers
• Humans
• In Vitro Techniques
• Male
• Receptors, Neurokinin-1 (metabolism)
• Substance P (metabolism)
• Tendons (metabolism)
• Young Adult