Estrogen Selectively Enhances TMJ Disc but Not Knee Meniscus Matrix Loss

Abstract

The preponderance of temporomandibular joint (TMJ) degenerative disorders in women and their early onset during reproductive years have implicated female sex hormones, particularly 17-β estradiol (E2), in the pathogenesis of these disorders. Nevertheless, the mechanisms by which E2 contributes to TMJ degenerative disorders and the reasons for its targeted effects on the TMJ but not other joints remain poorly understood. Here, we developed an ovariectomized mouse model in which systemic E2 concentrations mimicked those in cycling women, and we determined the effect of E2 on the targeted turnover of TMJ fibrocartilage matrix via E2-induced matrix metalloproteinases MMP9 and MMP13. Infusion of E2 and progesterone (P4; hormone control) over 7 d resulted in 5- and 8-fold greater serum E2 and P4 levels relative to controls, respectively, achieving systemic hormone levels similar to high baseline levels in cycling women. Administration of E2 but not P4 caused a significant loss of TMJ collagen and glycosaminoglycans, which was accompanied by amplification of ERα and specific increases in MMP9 and MMP13 expression. This dose of E2 had no effect on knee meniscus fibrocartilage, demonstrating the specificity of the degradative effect of E2. Dose-response experiments showed a greater sensitivity and a higher peak induction of MMP9 and MMP13 in TMJ fibrocartilaginous cells than knee meniscus cells to E2, providing an explanation for the differential responses of these tissues to E2. Using MMP9- and MMP13-null mice, we observed no discernible effects of each proteinase individually to E2-mediated TMJ matrix loss but noted a significant compensatory reciprocal induction of each MMP by E2 in the absence of the other. The redundancy in E2’s induction of MMP9 and MMP13 suggests that the proteinases may together contribute to E2-mediated TMJ fibrocartilage loss. These results advance our understanding of E2-mediated upregulation of MMP9 and MMP13 on fibrocartilage matrix turnover targeted to the TMJ.

Nonlinear Relationship between Temporomandibular Joint Disc Displacement Distance and Disc Length: A Magnetic Resonance Imaging Analysis

“…Similar to past studies [ 27 , 28 ], the female subjects dominated the present study as they are more predisposed toward TMJ internal degeneration induced by female sex hormones [ 29 , 30 ] and gender-related differences in joint structure [ 31 ]. Patients with ADDWoR and patients with Class 3 discs were significantly older.…”

Associations among Orthodontic History, Psychological Status, and Temporomandibular-Related Quality of Life: A Cross-Sectional Study

“…Through binary regression analysis, female was found to associate with higher prevalence of TMD, in accordance with previous studies [ 39 , 40 ]. This might be the result that TMJ is a potential target organ for estrogen, which promotes arthropathy and fascial pain [ 41 ]. Besides, adjustment of income made the estimated effect of OS on temporomandibular quality of life greater than the nonadjusted model.…”

TMD in Females with Menstrual Disorders

“…The pathomechanism of influence of female reproductive hormones on masticatory organ is not fully known. 17-β estradiol (E2) plays a major role in the pathogenesis of the masticatory organ lesions in women of childbearing age; it induces the production of matrix metalloproteinase (MMP9 and MMP13) in the TMJ fibrocartilage and leads to its destruction [ 43 , 52 , 53 , 54 ]. Regrettably, the mechanisms of E2 destructive influence remain little recognized [ 48 ].…”