Estrogen Selectively Enhances TMJ Disc but Not Knee Meniscus Matrix Loss.

Area of Science:

• Biochemistry
• Endocrinology
• Orthopedics

Background:

• Temporomandibular joint (TMJ) degenerative disorders disproportionately affect women, with onset during reproductive years, implicating 17-β estradiol (E2).
• Mechanisms of E2's role in TMJ pathogenesis and its targeted effects on TMJ over other joints remain unclear.

Purpose of the Study:

• To investigate the effect of E2 on TMJ fibrocartilage matrix turnover.
• To elucidate the role of E2-induced matrix metalloproteinases (MMPs) in TMJ degeneration.

Main Methods:

• Developed an ovariectomized mouse model with E2 levels mimicking cycling women.
• Administered E2 and progesterone (P4), assessing TMJ and knee meniscus fibrocartilage.
• Utilized MMP9- and MMP13-null mice to examine the compensatory roles of these proteinases.

Main Results:

• E2 administration significantly reduced TMJ collagen and glycosaminoglycans, increasing ERα, MMP9, and MMP13 expression.
• E2 did not affect knee meniscus fibrocartilage, indicating tissue-specific effects.
• TMJ cells showed higher sensitivity to E2-induced MMP9 and MMP13 upregulation than knee meniscus cells.
• Mice lacking either MMP9 or MMP13 showed compensatory induction of the other, suggesting functional redundancy.

Conclusions:

• E2 specifically targets TMJ fibrocartilage, inducing matrix degradation via MMP9 and MMP13.
• The differential sensitivity of TMJ cells explains E2's targeted effects.
• Redundancy between MMP9 and MMP13 contributes to E2-mediated TMJ matrix loss.