title: Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth.
abstract: OBJECTIVE
  Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice.
  
  
  METHODS
  21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed.
  
  
  RESULTS
  In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression.
  
  
  CONCLUSIONS
  Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kamiya
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Polur
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.affiliation: Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Choi
authors.affiliation: Division of Orthodontics, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Kalajzic
authors.affiliation: Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: H
authors.initials: H
authors.lastname: Drissi
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY, USA. Electronic address: jc3835@columbia.edu.
authors.forename: S
authors.initials: S
authors.lastname: Wadhwa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002358:Cartilage, Articular / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008335:Mandibular Condyle / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D013704:Temporomandibular Joint / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047629:Estrogen Receptor beta; D004967:Estrogens; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse; D012313:RNA
keywords: Chondrocyte; Estrogen receptor; Temporomandibular joint