TY - JOUR
T1 - In silico study of principal sex hormone effects on post-injury synovial inflammatory response
AU - Powell, Bethany
AU - Szleifer, Igal
AU - Dhaher, Yasin Y.
N1 - Publisher Copyright:
© 2018 Powell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/12
Y1 - 2018/12
N2 - Following an anterior cruciate ligament injury, premenopausal females tend to experience poorer outcomes than males, and sex hormones are thought to contribute to the disparity. Evidence seems to suggest that the sex hormones estrogen, progesterone, and testosterone may regulate the inflammation caused by macrophages, which invade the knee after an injury. While the individual effects of hormones on macrophage inflammation have been studied in vitro, their combined effects on post-injury inflammation in the knee have not been examined, even though both males and females have detectable levels of both estrogen and testosterone. In the present work, we developed an in silico kinetic model of the post-injury inflammatory response in the human knee joint and the hormonal influences that may shape that response. Our results indicate that post-injury, sex hormone concentrations observed in females may lead to a more pro-inflammatory, catabolic environment, while the sex hormone concentrations observed in males may lead to a more anti-inflammatory environment. These findings suggest that the female hormonal milieu may lead to increased catabolism, potentially worsening post-injury damage to the cartilage for females compared to males. The model developed herein may inform future in vitro and in vivo studies that seek to uncover the origins of sex differences in outcomes and may ultimately serve as a starting point for developing targeted therapies to prevent or reduce the cartilage damage that results from post-injury inflammation, particularly for females.
AB - Following an anterior cruciate ligament injury, premenopausal females tend to experience poorer outcomes than males, and sex hormones are thought to contribute to the disparity. Evidence seems to suggest that the sex hormones estrogen, progesterone, and testosterone may regulate the inflammation caused by macrophages, which invade the knee after an injury. While the individual effects of hormones on macrophage inflammation have been studied in vitro, their combined effects on post-injury inflammation in the knee have not been examined, even though both males and females have detectable levels of both estrogen and testosterone. In the present work, we developed an in silico kinetic model of the post-injury inflammatory response in the human knee joint and the hormonal influences that may shape that response. Our results indicate that post-injury, sex hormone concentrations observed in females may lead to a more pro-inflammatory, catabolic environment, while the sex hormone concentrations observed in males may lead to a more anti-inflammatory environment. These findings suggest that the female hormonal milieu may lead to increased catabolism, potentially worsening post-injury damage to the cartilage for females compared to males. The model developed herein may inform future in vitro and in vivo studies that seek to uncover the origins of sex differences in outcomes and may ultimately serve as a starting point for developing targeted therapies to prevent or reduce the cartilage damage that results from post-injury inflammation, particularly for females.
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U2 - 10.1371/journal.pone.0209582
DO - 10.1371/journal.pone.0209582
M3 - Article
C2 - 30596697
AN - SCOPUS:85059273159
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 12
M1 - e0209582
ER -