Periodontitis is a highly prevalent disease characterized by
inflammation and destruction of tooth-supporting tissues that leads to
tooth loss in extreme situations. Elucidating the underlying mechanisms of
periodontitis pathogenesis and progression will establish the groundwork for developing effective treatment strategies. Recently, evidence concerning the role of ferroptosis in
periodontitis progression has emerged. Osteogenic lineage cells are key regulators of bone remodeling. Osteogenic cell death, as observed in experimental
periodontitis models, disrupts the balance between
bone resorption and bone formation. However, whether the osteogenic lineage undergoes ferroptosis during
periodontitis and the corresponding effect on
periodontitis progression remain elusive. Here, we investigated cell-specific ferroptosis within the alveolar bone in a murine
periodontitis model. Through immunofluorescence double staining and immunohistochemistry, we identified ferroptotic osteocytes and osteoblasts in inflammatory alveolar bone. Next, in vivo administration of
erastin or
liproxstatin-1 was conducted to either induce or inhibit ferroptosis, respectively. Severe
bone resorption and
inflammation, accompanied by increased osteoclast formation and impaired osteogenic potential were detected following ferroptosis activation. Subsequently, we carried out in vitro experiments on osteocytes and further verified that ferroptosis enhanced the osteocytic expression of RANKL and
IL-6. These findings suggest that ferroptosis occurring within the osteogenic lineage acts as a catalyst in the progression of
periodontitis by stimulating osteoclastogenesis through the secretion of inflammatory
cytokines and inhibiting osteoblastic function, providing insights into ferroptosis-induced alterations in microenvironment-based intercellular communication. Ferroptosis is a promising target for controlling
inflammation and preventing
bone resorption in
periodontitis.