The possible role of sirtuin 5 in the pathogenesis of apical periodontitis

Objectives We investigated the relation between expression of sirtuin 5 (SIRT5) in osteoblastic cells and progression of apical periodontitis. The role of SIRT5 in hypoxia‐induced reactive oxygen species (ROS) formation and osteoblast apoptosis was also examined. Materials and Methods Progression of rat apical periodontitis was monitored by conventional radiography and microcomputed tomography. SIRT5 and oxidative stress biomarker 8‐OHdG in bone‐lining cells were assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling was used to demonstrate apoptosis. In primary human osteoblasts cultured under hypoxia, Western blot was used to analyze SIRT5 expression and cleavage of pro‐caspase 3 and poly(ADP‐ribose) polymerase (PARP). SIRT5 was overexpressed through lentiviral technique. ROS formation and mitochondrial membrane potential changes were assessed by MitoSOX‐Red and JC‐1 fluorescence, respectively. Immunofluorescence microscope was used to evaluate mitochondrial release of cytochrome c. Results In rat apical periodontitis, disease progression was accompanied by decreased expression of SIRT5, increased oxidative stress, and enhanced apoptosis in bone‐lining cells. SIRT5 was suppressed in cultured osteoblasts under hypoxia. SIRT5 overexpression ameliorated hypoxia‐enhanced ROS formation, mitochondrial depolarization, cytochrome c leakage, activation of caspase‐3, and PARP fragmentation. Conclusions SIRT5 is able to alleviate hypoxia‐enhanced osteoblast apoptosis. SIRT5 augmentation may have therapeutic potential for apical periodontitis.