Insights into taurine therapy for periodontitis: Targeting osteocyte ferroptosis to mitigate obesity-exacerbated bone damage.

Obesity is a major systemic risk factor for periodontitis and is associated with increased alveolar bone destruction. However, the mechanisms by which obesity-related metabolic stress aggravates periodontal bone loss remain poorly understood. This study sought to elucidate whether osteocyte ferroptosis represents a key mechanistic driver of obesity-exacerbated periodontal bone destruction and whether taurine alleviates this pathology, at least in part, by suppressing ferroptosis. We established a mouse model of diet-induced obesity with experimental periodontitis and an in vitro MLO-Y4 osteocyte model exposed to palmitic acid and lipopolysaccharide to recapitulate the combined lipotoxic and inflammatory microenvironment of obesity-associated periodontitis. Compared with periodontitis alone, obesity significantly exacerbated alveolar bone loss, osteocyte-mediated remodeling imbalance, and systemic inflammatory burden. RNA-sequencing and molecular analyses revealed increased osteocyte ferroptosis, characterized by severe lipid peroxidation, iron dyshomeostasis, and impaired antioxidant defense. Notably, obese mice with periodontitis exhibited systemic taurine deficiency. Taurine supplementation markedly attenuated alveolar bone loss, restored osteocyte-mediated remodeling balance, and robustly suppressed osteocyte ferroptosis both in vivo and in vitro. Importantly, co-administration of the ferroptosis activator erastin partially abolished the protective effects of taurine, further supporting a ferroptosis-dependent protective mechanism. Our findings reveal osteocyte ferroptosis as a previously unrecognized pathogenic mechanism in obesity-exacerbated periodontal bone destruction. Additionally, we identify taurine as a promising therapeutic strategy targeting osteocyte ferroptosis, offering new mechanistic insights and translational potential for managing obesity-associated periodontitis.