Objective Temporomandibular joint 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 WT and ER beta KO mice. Materials and 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 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. Conclusion Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.
Both OTM and Relapse groups exhibited a decreased number of GFP-labeled cells in areas of compression and tension. There was significant PDL apoptosis in regions under compressive forces following OTM and to a lesser extent following relapse.
Objective 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. Methods 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. Results 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. Conclusions 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.
The mandibular condylar cartilage (MCC) is derived from periosteum and undergoes endochondral ossification during growth. Growth and remodeling of periosteal-derived bone is known to be modulated by estrogen signaling. Estrogen receptor alpha (ERα) and beta (ERβ) are the two main transmembrane receptors that mediate the majority of estrogen’s effects. In the appendicular skeleton, estrogen via ERα receptor signaling has been shown to mediate endochondral growth plate fusion in both males and females. However, the role of ERα in mediating growth of the mandibular condylar cartilage is unknown. To this end, we have characterized mandibular condylar cartilage growth in young (49 day-old) and adult (9 month-old) male ERαKO mice. In young mice, a significant increase in the number of mandibular condylar cartilage cells and a significant decrease in the expression of Col10, Runx2, and DMP1 was observed in the male ERαKO mice compared to WT. In 9 month old mice, we found a similar increase in the number of cells but no change in osteoarthritic histological scoring in ERαKO mice compared to WT mice. In summary, estrogen plays a role in mediating mandibular condylar maturation in young male mice. However, according to this study, it does not play a role in mediating long term growth or age-related mandibular condylar cartilage degeneration in males.
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