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Critical Reviews™ in Biomedical Engineering
SJR: 0.243 SNIP: 0.376 CiteScore™: 0.79

ISSN Print: 0278-940X
ISSN Online: 1943-619X

Critical Reviews™ in Biomedical Engineering

DOI: 10.1615/CritRevBiomedEng.2016016590
pages 401-428

Review of the Multiscale Effects of Female Sex Hormones on Matrix Metalloproteinase−Mediated Collagen Degradation

Bethany S. Powell
Department of Biomedical Engineering, Northwestern University, Evanston, IL
Yasin Y Dhaher
Department of Biomedical Engineering, Northwestern University, Physical Medicine and Rehabilitation Department, Evanston, IL, and Rehabilitation Institute of Chicago, Sensory Motor Performance Program, Chicago, IL
Igal G. Szleifer
Department of Biomedical Engineering and Department of Chemistry, Northwestern University, Evanston, IL


Collagenases and gelatinases regulate many physiological processes and are involved in the pathogenesis and progression of various disease states, such as osteoarthritis, renal fibrosis, and atherosclerosis. These enzymes belong to the matrix metalloproteinase (MMP) family and are regulated by a number of factors, including sex hormones. Estrogen, relaxin, and progesterone can alter the balance between tissue degradation and repair by modulating MMPs, leading to gender disparities in many MMP-related disease states. In these diseases, MMPs initiate collagen degradation at the nanoscale when they cleave and denature collagen molecules. However, the net effect on tissue is generally observed at the macroscale. To understand how nanoscale events lead to macroscale changes, we must examine the intermediate scales. In this article, we review the literature that examines the effects of estrogen, relaxin, and progesterone on MMP production and activity, connecting the nanoscale, microscale, and macroscale details to relevant disease states.

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