Estrogen and altered loading regulate chondrogenesis of the mouse TMJ

Objective: Temporomandibular joint disorders (TMD) predominantly affect women of childbearing ages. It has been previously established that altered loading of the temporomandibular joint (TMJ) may be one of the major etiological factors for the development of TMD. Thus, while correlations between estrogen deficiency and mechanical loading during bone loss have been postulated, possible interactions between estrogen and mechanical loading of the TMJ remain unknown. We have recently described an altered loading TMJ mouse model using female CD-1 mice. Therefore, in this study we examined if gender or ovariectomy in CD-1 mice caused differences in response to altered masticatory loading.

Methods: 21-day-old male (n=10), female (n=10) and ovariectimized female (n=6) CD-1 mice were divided into two groups. The mice were either fed a normal pellet diet (normal loading) or a soft diet and had their incisors trimmed out of occlusion (altered loading) for 4 weeks. Gene expression was performed for Prg4, Pthrp, Sox9, Col2, Ihh, Col10, and Vegf, by real time PCR analysis and Col2 protein expression was determined by immunohistochemistry.

Results: In female mice, altered loading resulted in significant decreases in the mRNA expression of Col2, Sox 9, Col 10, Ihh and Vegf and a significant decrease in Col2 protein expression compared to the normal loading group. In contrast, in male mice altered loading induced significant decreases in the mRNA expression of only Col10, and Ihh and in ovariectimized female mice altered loading did not cause a significant decrease in Col2 protein expression compared with the normal loading group

Conclusions: Altered loading caused a more profound decrease in chondrocyte differentiation markers in female mice compared to male mice and ovariectimized female mice which maybe due to the effect of estrogen. This work was supported by NIDCR K-22 DE017193 grant and American Association of Orthodontists Foundation Faculty Development Award to SW.