Combination of estrogen deficiency and excessive mechanical stress aggravates temporomandibular joint osteoarthritis in vivo

Objective: It has been suggested that degenerative conditions of the temporomandibular joint (TMJ), such as osteoarthritis (OA) and progressive condylar resorption, are caused by multiple etiological factors, such as hormonal imbalance and excessive mechanical stress. However, it is unclear whether these factors interrelate in the degenerative process of the condyle. The aim of this study was to observe the effects of combined hormonal imbalance and excessive mechanical stress on the condyle using a mouse model. Materials and methods: Ovariectomy (OVX) was performed in 8-week-old female mice. Three weeks after OVX, a build-up resin was bonded to the right maxillary molars to create imbalanced occlusion (increased occlusal vertical dimension, iOVD). Mice were divided into four groups: control, OVX, iOVD, and OVX + iOVD. Results: Histomorphometric analysis showed the lowest cartilage thickness and the highest TMJ-OA score in the OVX + iOVD group. Bone structural analysis showed significantly lower subchondral bone mass in all experimental groups. Additionally, the OVX + iOVD group showed up-regulated osteoclastic activity and increased apoptosis in the condyle. Gene expression analysis showed significantly elevated expression of pre-inflammatory cytokines in the OVX + iOVD group. These data showed that the OVX + iOVD group exhibited the most severe inflammatory TMJ-OA. Upregulation of ER alpha and activation of the ERK pathway was observed in the OVX + iOVD group. Conclusions: Additive effects of estrogen deficiency and excessive mechanical stress on the condyle exacerbate TMJ-OA. Furthermore, estrogen deficiency and excessive mechanical stress combined may exacerbate TMJ-OA though activation of the ERK pathway.