title: The effect of estrogen on ovine anterior cruciate ligament fibroblasts: cell proliferation and collagen synthesis.
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.
  
  
  OBJECTIVE
  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 17beta-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 (3)H-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 17beta-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.
authors.affiliation: Hospital for Special Surgery, New York, New York 10021, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Seneviratne
authors.forename: Erik
authors.initials: E
authors.lastname: Attia
authors.forename: Riley J
authors.initials: RJ
authors.lastname: Williams
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
authors.forename: Jo A
authors.initials: JA
authors.lastname: Hannafin
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000502:physiology*; D000070598:Anterior Cruciate Ligament Injuries; D049109:Cell Proliferation; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D004967:Estrogens / Q000494:pharmacology*; D005347:Fibroblasts / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology; D012307:Risk Factors; D012756:Sheep
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D003094:Collagen