Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading

Abstract

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.

Estrogen signaling impacts temporomandibular joint and periodontal disease pathology

“…Further, ERβ inhibits mandibular condyle growth by promoting fibrocartilage turnover [71]. On the other hand, ERβ does not play a significant role on the young male mandibular condylar fibrocartilage [72]. Based on these data, future studies focused on the targeted role of ER agonists and/or antagonists to control cell proliferation and matrix production are warranted.…”

Morfología y Fisiopatología del Fibrocartílago de la ATM. Revisión sistemática.

“…Como muchas enfermedades articulares degenerativas, presentan alta frecuencia en el sexo femenino asociado al rol regulador de las hormonas sexuales involucradas en el control metabólico de estos tejidos (24,38) y alta prevalencia en edad fértil, (18-45 años), a diferencia de otras enfermedades degenerativas articulares que se observan principalmente en mujeres post menopáusicas (39) . Las causas de esta distribución de sexo y edad se asocian al potencial rol de las hormonas reproductivas femeninas, que se explica por los niveles plasmáticos hormonales y las diferentes concentraciones de receptores de estrógenos (ER-α y β), en los tejidos articulares de mujeres (40,41) .…”

Effect of Mechanical Stress on Rheumatoid Arthritis of the Temporomandibular Joint: a Morphological and Histological Evaluation

“…Therefore, we designed a similar device for the mouse model. Unlike the TMJ, which is composed of hyaline cartilage, the mandibular condyle cartilage is composed of brocartilage derived from periosteal tissue, so the size and characteristics of the tissue are adjusted to adapt to changes in load (27). As the device we used in this study used a metal plate for the occlusal part, it did not wear because of occlusion, and its thickness remained constant during the device wearing period.…”