title: Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.
abstract: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERβ) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERβ signaling in mediating DOL effects in male mice to further decipher sex differences.
  
  
  
  Male 21 day-old WT and ERβKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ.
  
  
  
  ERβKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes.
  
  
  
  The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.
authors.affiliation: Columbia University Division of Orthodontics, New York, NY, USA; Department of Biomedical Engineering, New York, NY, USA. Electronic address: Jlr2228@columbia.edu.
authors.forename: J L
authors.initials: JL
authors.lastname: Robinson
authors.affiliation: Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Cass
authors.affiliation: Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Aronson
authors.affiliation: Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Choi
authors.affiliation: Columbia University Division of Orthodontics, 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: R
authors.initials: R
authors.lastname: Buttenbaum
authors.affiliation: New England Musculoskeletal Institute, Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: H
authors.initials: H
authors.lastname: Drissi
authors.affiliation: Department of Biomedical Engineering, New York, NY, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Lu
authors.affiliation: Columbia University Division of Orthodontics, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Columbia University Division of Orthodontics, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wadhwa
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D024043:Collagen Type II / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D015870:Gene Expression; D008297:Male; D008335:Mandibular Condyle / Q000000981:diagnostic imaging / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D012737:Sex Factors; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016474:Weight-Bearing / Q000502:physiology; D055114:X-Ray Microtomography
chemical_list: D024043:Collagen Type II; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol
keywords: Decreased occlusal loading; Estradiol; Estrogen receptor β; Mandibular condylar cartilage; Sex differences; Temporomandibular joint