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Document Title: Seneviratne-AJSM-Oct04
Article Title: The Effect of Estrogen on Ovine Anterior Cruciate Ligament Fibroblasts Cell Proliferation and Collagen Synthesis
Authors: Aruna Seneviratne, MD, Erik Attia, Riley J. Williams, MD, Scott A. Rodeo, MD and Jo A. Hannafin, MD, PhD,
Publication: American Journal of Sports Medicine, Baltimore, Maryland
Date: October 2004
Volume 32, pages 1613-1618
(Figures included. Reference-denoting numbers appear in the same point size as the document text.)
This is a very interesting investigation into the effect of estrogen on ligaments. The authors caution about extrapolating from sheep to humans. It is also interesting to note that estrogen, when released prior to and during labour, serves to weaken ligaments and therefore to facilitate childbirth. The authors conclude, however, that the two-to-three-day estrogen spike during the luteal phase of the human female period would probably not be of sufficient duration to result in significant weakness of the ACL in the knee. But they also note that further investigation is needed. (Note, too, that the biomechanics of the human body are quite different from those of the sheep. A sheep walks on four legs, and so there is less stress at the knee when it changes direction. If a sheep were to run at the same speed and change direction at the same rate as an athletic human, the sheep would be at far less risk of tearing an ACL. Additionally, the sheep's centre of gravity is substantially lower than that of a human.)
Abstract: Estrogen has been implicated as a causal factor for anterior cruciate ligament injuries in women. Studies have demonstrated a decrease in anterior cruciate ligament fibroblast proliferation and collagen synthesis at supraphysiologic levels of estrogen in a rabbit model.
Hypothesis: The authors hypothesized that physiologic levels of estrogen would have no significant effect on anterior cruciate ligament fibroblast proliferation and collagen synthesis in an ovine model.
Methods: Anterior cruciate ligament fibroblasts were isolated from sheep knees using routine cell culture methods. The cells were exposed to 17ß-estradiol at physiologic concentrations of 2.2, 5, 15, 25, 250, and 2500 pg/ml. Cell proliferation was determined by cell counts on days 4 and 6. Collagen synthesis was determined by 3H-proline incorporation on day 4. Immunohistochemistry was performed to detect estrogen receptors.
Results: Immunohistochemistry demonstrated the presence of estrogen receptors in ovine anterior cruciate ligament fibroblasts. There was no significant difference in anterior cruciate ligament fibroblast proliferation or collagen synthesis regardless of 17ß-estradiol concentration.
Conclusions: Based on results of this study, and given the low turnover of collagen in ligaments, it is unlikely that a 2- to 3-day per month increase in circulating estrogen would result in rapid, clinically significant alterations in material properties of the anterior cruciate ligament in vivo. The etiology of noncontact anterior cruciate ligament injuries is complex and multifactorial in nature, meriting further investigation.
Key Words: estrogen, collagen synthesis, anterior cruciate ligament, cell proliferation, female athlete
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