Targeting mitochondrial fission to ameliorate apoptosis of gingival fibroblasts: novel perspectives on inflammatory gingival recession prevention.

Abstract

Gingival recession currently lacks effective strategies for prevention and treatment. Excessive apoptosis of gingival fibroblasts (GFs) compromises the biosynthetic capacity of periodontal tissues, thereby accelerating the progression of gingival recession. Mitochondria play a critical role in the apoptotic pathway and mitochondrial dynamics are essential for maintaining mitochondrial function. However, the specific role of mitochondrial dynamics in regulating GFs apoptosis and its contribution to gingival recession remains unclear. Emerging evidence suggests that mitochondrial dynamics, specifically the balance between mitochondrial fission and fusion, are essential for maintaining mitochondrial function. Excessive mitochondrial fission may lead to mitochondrial fragmentation, loss of mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) accumulation, ultimately resulting in cellular damage. We utilized lipopolysaccharide (LPS) to mimic the inflammatory stimulation of GFs in vitro and established a novel in vivo model that integrates a bone defect with ligature-induced inflammation to recapitulate and study gingival recession. LPS not only induced significant inflammation and apoptosis in GFs but also triggered an imbalance in mitochondrial dynamics, characterized by enhanced fission, decreased MMP, and impaired ATP production. Notably, Mdivi-1 treatment reversed these detrimental effects. Consistently, in animal models, Mdivi-1 alleviated gingival inflammation, enhanced gingival connective tissue fiber density, and suppressed mitochondrial fission and apoptosis of fibroblasts, ultimately mitigating the severity of gingival recession. In conclusion, this study investigates the role of mitochondrial dynamics in inflammatory gingival recession and provides its inhibition as a potential strategy for prevention.