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Effects of estrogen, progesterone, and relaxin on gene expression and collagen remodeling enzyme activities in primary human tendon cells Tuin, Ho Shun

Abstract

This study investigates the impact of various hormones—estradiol, estriol, progesterone, and relaxin—on tendon cell biology under both non-stretched and mechanically active conditions. Gene expression changes, extracellular remodeling enzyme activities, and collagen content were analyzed. Under non-stretched conditions, estradiol decreased elastin (ELN) and decorin (DCN) expression, while relaxin increased type I collagen (COL1A1), lysyl oxidase (LOX), and tissue inhibitor of metalloproteinases 3 (TIMP3) expression, suggesting enhanced collagen synthesis and cross-linking. Combined hormone treatment in non-stretched conditions led to decreases in COL1A1, LOX, matrix metalloproteinase 13 (MMP13), TIMP3, and LOX activity, indicating potential weakening of tendon structure, reflecting changes seen during pregnancy. Under mechanically active conditions, estradiol increased COL3A1 expression and decreased LOX activity, which may indicate an early reparative response that could enhance flexibility but potentially compromise structural integrity. Relaxin showed signs of adaptive remodeling, with decreases in ELN and increases in TIMP3 expression, suggesting a complex role in tendon injury modulation. The combined hormone treatment resulted in decreased angiopoietin-like-4 (ANGPTL4) and TIMP3 expression, indicating a mixed influence on tendon injury response and repair mechanisms. In conclusion, the influence of sex hormones on tendon cells is context-dependent, varying with mechanical loading and hormone combinations, and may play a significant role in modulating injury risk.

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Attribution-NonCommercial-NoDerivatives 4.0 International