GSE110300
Next Generation Sequencing Provides Transcriptional Analysis for Estradiol Effects in Skeletally Immature (7-weeks old) Female WT and Estrogen Receptor Alpha Knockout Mice
Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERa) during growth and maturity of the joint. Young and mature WT and ERaKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERa on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERa promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage. Overall design: Examination and comparison of the role of 17ß-estradiol (E2) via estrogen receptor alpha (Eralpha) on the transcriptional regulation of genes in the mandibular condylar fibrocartialge of skeletally immature (7-week old) female mice.