Osteocyte dysregulation in periodontitis: Pathological mechanisms and therapeutic potential

Periodontitis, a chronic inflammatory disease driving alveolar bone destruction, is critically mediated by osteocyte dysregulation. This review synthesizes current evidence revealing that osteocyte-derived RANKL and sclerostin actively promote osteoclastogenesis while suppressing osteoblast activity, directly accelerating bone resorption. Osteocyte apoptosis, ferroptosis, and senescence further exacerbate inflammation through cytokine cascades (e.g., IL-6, TNF-α) and impair regenerative capacity. Therapeutically, targeting osteocytes with anti-RANKL (e.g., denosumab) or anti-sclerostin antibodies (e.g., romosozumab) significantly reduces osteoclast activation and bone loss in preclinical models, while activation of the Notch signaling pathway enhances osteocyte survival and promotes bone formation. Collectively, these findings highlight osteocyte-centered signaling as a promising therapeutic avenue for restoring bone homeostasis and underscore the need for further research to translate these mechanisms into clinical interventions for periodontitis.