Abstract
Periodontitis is a chronic inflammatory disease characterized by progressive destruction of alveolar bone. The most critical mechanism underlying alveolar bone destruction is the imbalance of bone homeostasis, where osteoblast-mediated bone matrix synthesis plays an important role in regulating bone homeostasis. Regulated cell death is instrumental in both the inflammatory microenvironment and the regulation of bone homeostasis. Chronic inflammation, oxidative stress, and other factors can be directly involved in mitochondrial and death receptor-mediated signaling pathways, modulating B-cell lymphoma 2 family proteins and cysteine aspartic acid specific protease (caspase) activity, thereby affecting osteoblast apoptosis and alveolar bone homeostasis. Chronic inflammation and cellular damage induce osteoblast necroptosis via the RIPK1/RIPK3/MLKL signaling pathway, exacerbating the inflammatory response and accelerating alveolar bone destruction. Stimuli such as pathogenic microorganisms and cellular injury may also activate caspase-1-dependent or independent signaling pathways and gasdermin D family proteins, promoting osteoblast pyroptosis and releasing pro-inflammatory cytokines to mediate alveolar bone damage. Iron overload and lipid peroxidation in periodontitis can trigger ferroptosis in osteoblasts, impacting their survival and function, ultimately leading to bone homeostasis imbalance. This article focuses on the mechanism of periodontal disease affecting bone homeostasis through regulatory cell death, aiming to provide research evidence for the treatment of periodontitis and alveolar bone homeostasis imbalance.