Role of Estrogen in Monosodium Iodoacetate-induced TMJ Osteoarthritis

Objectives: Approximately 1% of the US population suffers from TMJ-OA. Unlike other joints, TMJ-OA predominantly afflicts middle-age women suggesting a role of estrogen in the disease process. However, the role of estrogen receptors in mediating this process is unknown. Thus, the specific aims of this study were to determine the role of Estrogen receptor alpha in mediating MIA-induced TMJ-OA as well as determine the role of ER alpha in mediating MIA- induced TMJ degradation.
Methods: 15-week-old male WT and ER alpha KO mice were sectioned and treated with placebo or estradiol. Half the mice received monosodium iodoacetate and the other half vehicle. Changes to MCC thickness, cell number, and cell density were measured using histomorphometric methods. TMJ degradation was evaluated through real-time PCR analysis and immunohistochemical staining for gene expression of several matrix metalloproteinases, including MMP9 and MMP13.
Results: No statistical significance was observed in the MCC thickness or cell number counts between the MIA-induced WT and ER alpha KO mice. Additionally, no significant difference was found between levels of various pro-apoptotic genes. This study is restricted by a single model of MIA-induced TMJOA. The sample size was rather small for histopathological evaluation. A larger sample size along with consideration of other female hormones could be examined.
Conclusions: Due to advances in selective estrogen receptor modulator pharmacological therapies, greater understanding of the role of the estrogen receptor in mediating TMJ-OA is critical. Estrogen expression and activity still remains a key issue as it acts on multiple different systems. There is a need for a new, effective and well-tolerated treatment that lacks the negative side effects such as TMJ-OA potentiation and thromboembolism seen in estrogen therapy. Such a novel therapy could include an estrogen receptor agonist with a distinctive mode of action.