Relaxin and Estrogen Modulate Targeted Matrix Loss in TMJ Disc

Objective: Because TMJ disorders are prevalent in woman of reproductive age, it has been hypothesized that female hormones contribute to the initiation or progression of these disorders. Our purpose was to establish a mouse model for manipulation of systemic hormone concentrations, and to dissect the contributions that relaxin, estrogen, and progesterone make to extracellular matrix turnover and matrix metalloproteinase (MMP) expression in TMJ fibrocartilage compared to that in the pubic symphysis and knee meniscus fibrocartilages. Methods: Twelve-week-old female C57BL/6 mice were bilaterally ovariectomized, one week following which osmotic pumps containing relaxin or estrogen or progesterone or combinations of these hormones were implanted subcutaneously. Six days later, the mice were euthanized, blood was collected and TMJ disc, pubic symphysis and knee meniscus were retrieved. Tissues were analyzed for collagen, glycosaminoglycan, MMPs, and hormone receptors, while the serum was assayed for the hormones. Results: Mice receiving hormone/s had serum concentrations of the three hormones similar to those found physiologically in cycling women. Relaxin and/or estrogen contributed to targeted and significant loss of collagen and glycosaminoglycan in TMJ disc and pubic symphysis fibrocartilages, but not the knee meniscus fibrocartilage. Progesterone attenuated estogen- or relaxin-mediated matrix loss in the TMJ disc and pubic symphysis. Estrogen contributed to increased levels of estrogen receptor-1, while relaxin treatment resulted in enhanced levels of relaxin receptors RXFP1 and RXFP2 in TMJ fibrocartilage. Finally, estrogen and/or relaxin treated mice had increased mRNA levels for MMP-9 and -13 in TMJ fibrocartilage. Conclusion: The findings show a targeted modulation of matrix loss by relaxin and estrogen concomitant to increased expression of their respective receptors and MMP-9 and -13 in TMJ fibrocartilage. These findings suggest that these two hormones may contribute selectively to degeneration of matrices from the TMJ disc possibly via upregulation of specific MMPs. (Supported by NIH/NIDCR RO1 DE018455)