title: Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum.
abstract: BACKGROUND
  Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum.
  
  
  METHODS
  Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated.
  
  
  RESULTS
  In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17β-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10(-9) M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol.
  
  
  CONCLUSIONS
  The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Chen
authors.forename: Chao-Kai
authors.initials: CK
authors.lastname: Hu
authors.forename: Pei-Ru
authors.initials: PR
authors.lastname: Chen
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Chen
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, Ming Chuan University, Taoyuan, Taiwan. chen.minghong@gmail.com.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chen
mesh_terms: D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017843:Ligamentum Flavum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011960:Receptors, Estrogen; D004958:Estradiol; D003094:Collagen; D058539:Phosphatidylinositol 3-Kinase; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13