title: Increased mandibular condylar growth in mice with estrogen receptor beta deficiency.
abstract: Temporomandibular joint (TMJ) disorders predominantly afflict women of childbearing age, suggesting a role for female hormones in the disease process. In long bones, estrogen acting via estrogen receptor beta (ERβ) inhibits axial skeletal growth in female mice. However, the role of ERβ in the mandibular condyle is largely unknown. We hypothesize that female ERβ-deficient mice will have increased mandibular condylar growth compared to wild-type (WT) female mice. This study examined female 7-day-old, 49-day-old, and 120-day-old WT and ERβ knockout (KO) mice. There was a significant increase in mandibular condylar cartilage thickness as a result of an increased number of cells, in the 49-day-old and 120-day-old female ERβ KO compared with WT controls. Analysis in 49-day-old female ERβ KO mice revealed a significant increase in collagen type X, parathyroid hormone-related protein (Pthrp), and osteoprotegerin gene expression and a significant decrease in receptor activator for nuclear factor κ B ligand (Rankl) and Indian hedgehog (Ihh) gene expression, compared with WT controls. Subchondral bone analysis revealed a significant increase in total condylar volume and a decrease in the number of osteoclasts in the 49-day-old ERβ KO compared with WT female mice. There was no difference in cell proliferation in condylar cartilage between the genotypes. However, there were differences in the expression of proteins that regulate the cell cycle; we found a decrease in the expression of Tieg1 and p57 in the mandibular condylar cartilage from ERβ KO mice compared with WT mice. Taken together, our results suggest that ERβ deficiency increases condylar growth in female mice by inhibiting the turnover of fibrocartilage.
authors.affiliation: Division of Orthodontics, Columbia University College of Dental Medicine, New York, NY 10032, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Manshan
authors.initials: M
authors.lastname: Xu
authors.forename: Achint
authors.initials: A
authors.lastname: Utreja
authors.forename: Thomas
authors.initials: T
authors.lastname: Choi
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
authors.forename: Sunil
authors.initials: S
authors.lastname: Wadhwa
mesh_terms: D000818:Animals; D002453:Cell Cycle; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008335:Mandibular Condyle / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
chemical_list: D047629:Estrogen Receptor beta; D007334:Insulin-Like Growth Factor I