Yosuke Kamiya, Jing Chen, Manshan Xu, Achint Utreja, Thomas Choi, Hicham Drissi, Sunil Wadhwa
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 with wild type (WT) female mice. This study examined female 7-, 49- and 120-day-old WT and ERβ knockout (KO) mice. There was a significant increase in mandibular condylar cartilage thickness, due to an increased number of cells, in the 49- 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, Pthrp and osteoprotegrin gene expression and a significant decrease in Rankl and 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 fibrocartilage turnover.