Traumatic occlusion aggravates bone loss during periodontitis and activates Hippo-YAP pathway

Abstract

Aim: This study aimed at exploring changes in YAP expression and their effect on periodontitis (PD) combined with traumatic occlusion (TO).

Materials and methods: BALB/cJ mice were used to establish a PD model by local administration of Porphyromonas gingivalis (P.g, ATCC 33277) and a TO model by occlusal elevation (OE) using composite resin bonding on the bilateral maxillary molar. The mouse fibroblast cell line (L929) and pre-osteoblast cell line (MC3T3-E1) were subjected to cyclic tensile/compressive stress and inflammatory stimuli (lipopolysaccharide from Escherichia coli) to verify in vivo results.

Results: Severe bone resorption was observed by microCT scanning in OE with P.g group, when compared to OE only and P.g only groups. Mechanical stress caused by OE activated the Hippo-YAP pathway in periodontal tissues and upregulated the expression of JNK/AP-1. OE with P.g further promoted the expression of YAP and JNK/AP1, leading to the upregulation of the JNK/AP-1 related inflammatory cytokines TNF-α and IL6. Similar results were obtained when osteoblasts were subjected to mechanical stress in vitro.

Conclusions: Our study demonstrated that periodontitis with TO caused severe inflammation-induced bone resorption. Activation of YAP and upregulation of JNK/AP-1 induced by TO potentially aggravated the symptoms of PD.

Keywords: Hippo pathway; YAP/TAZ; bone destruction; occlusal trauma; periodontitis.