Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway

Nicotine, a major component of tobacco, is implicated in the pathogenesis of periodontitis. However, the exact mechanisms through which nicotine exerts its harmful effects remain incompletely understood. This study investigates the impact of nicotine-induced mitochondrial fission on human periodontal ligament cells (hPDLCs). A range of assays, including MTT, immunofluorescence staining, flow cytometry, and western blotting, were utilized to evaluate hPDLC viability, apoptosis, mitochondrial fission, and function. Nicotine decreases hPDLC viability in a dose-dependent manner, leading to apoptosis, an elevated BAX/BCL-2 ratio, and cellular injury. Furthermore, nicotine induces phosphorylation of Drp1 at Ser616, which facilitates mitochondrial fission, elevates mitochondrial ROS production, reduces mitochondrial membrane potential, and lowers ATP generation, resulting in mitochondrial dysfunction. Inhibition of Drp1 phosphorylation by Mdivi-1 significantly alleviates mitochondrial fission and dysfunction, reduces nicotine-induced apoptosis, and promotes osteogenic differentiation. Nicotine activates c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity with SP600125 effectively prevents nicotine-induced mitochondrial fission, enhances cell viability, and inhibits Drp1 phosphorylation. • Mdivi-1 partially reduce nicotine-induced hPDLCs injury by affecting Drp1 levels. • Nicotine causes significant mitochondrial fragmentation in human pulp dental cells. • Nicotine reduced viability, and impaired osteogenic differentiation. • Nicotine activates c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity with SP600125 effectively prevents nicotine-induced mitochondrial fission.