periodontitis with traumatic occlusion
Periodontitis is a multifactorial inflammatory disease characterized by progressive alveolar bone resorption and subsequent tooth loss. Notably, coexisting traumatic occlusion aggravates periodontal inflammation and accelerates bone destruction. As a key mechanotransduction channel, Piezo1 mediates the responsiveness of human periodontal ligament fibroblasts (hPDLFs) to biomechanical stimuli. To investigate the role of Piezo1 in the pathogenesis of periodontitis associated with traumatic occlusion, we established a rat model integrating experimental periodontitis and traumatic occlusion. Histological analysis revealed that traumatic occlusion significantly downregulated the expression of Piezo1 in rat periodontal tissues, accompanied by reduced expression of osteogenic factors, including runt-related transcription factor 2 (RUNX2), as well as increased osteoclast activity and elevated levels of inflammatory mediators, such as interleukin-6 (IL-6). Consistent with in vivo experiments, the combined effects of lipopolysaccharide (LPS) and mechanical compressive stress overload down-regulated Piezo1 expression in hPDLFs, leading to impaired osteogenic capacity and an exacerbated inflammatory response. Mechanistically, RNA sequencing analysis identified the suppression of the mitogen-activated protein kinase (MAPK) signaling pathway as a key mechanism underlying the exacerbation of periodontitis induced by traumatic occlusion. Pharmacological activation of Piezo1 with Yoda1 restored the expression of p-ERK and p-JNK, while simultaneously enhancing osteogenic capacity. These findings demonstrate that traumatic occlusion accelerates periodontitis progression by inhibiting the Piezo1-mediated MAPK signaling pathway, suggesting that targeted Piezo1 activation may serve as a promising therapeutic strategy for alleviating periodontal destruction caused by traumatic occlusion.