Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

UNLABELLED: Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration. OBJECTIVE: To determine whether pharmaceutical glucocorticoids induce senescence in tenocytes. METHODS: Features of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection. RESULTS: Dexamethasone treatment of tenocytes resulted in an increased percentage of SA-βgal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro. CONCLUSION: As cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.

Original publication




Journal article


Ann Rheum Dis

Publication Date





1405 - 1413


Chondrocytes, Corticosteroids, Fibroblasts, Inflammation, Tendinitis, Adult, Aged, Cell Cycle, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p21, Dexamethasone, Female, Gene Knockdown Techniques, Glucocorticoids, Humans, In Vitro Techniques, Male, Middle Aged, Rotator Cuff, Signal Transduction, Sirtuin 1, TOR Serine-Threonine Kinases, Tendinopathy, Tendons, Tumor Suppressor Protein p53, beta-Galactosidase