Remodeling of the extracellular matrix (ECM) is required for the proper healing, strengthening, and maintenance of tendon tissue. There are well documented sex differences in tendon injury rates and healing outcomes, but the influence of sex on ECM remodeling is not well understood. Sex differences are often attributed to innate differences in tissue structure, resident cell signaling, or the influence of sex hormones, but these factors are rarely decoupled. Estrogen (17β-estradiol) and progesterone (P4) receptors are expressed in tendon tissue, and thus could participate in the remodeling process, but studies are extremely limited. The objective of this work is to address whether innate sex differences are present in tendon remodeling and to determine the individual and combined roles of estrogen and progesterone in the remodeling process. We utilized a tendon explant model with the flexor digitorum longus (FDL) of young adult male and female mice to explore cell behavior without disruption to the native environment and cultured them in various mechanical and hormonal conditions. We found innate sex differences in tendon remodeling, demonstrating possible chromosomal impacts on tendon tissue and mechanics. We also demonstrate sex- and strain-dependency in response to exogenous hormone delivery. Finally, we created a novel in vitro model of the murine estrous cycle and for the first time revealed that hormonal fluctuations regulate specific aspects of ECM turnover in a cyclic manner. This work is key in understanding the differences in injury prevalence and healing outcomes described in the literature and lays a foundation for exciting advances in the field of women’s health.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48887 |
| Date | 24 May 2024 |
| Creators | Sander, Allison M. |
| Contributors | Connizzo, Brianne K. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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