Deletion of vitamin D receptor exacerbated temporomandibular joint pathological changes under abnormal mechanical stimulation.

AIMS

Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration.

MAIN METHODS

Mice ablated for Vdr (Vdr) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined.

KEY FINDINGS

Vdr mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr chondrocytes.

SIGNIFICANCE

VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.