Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues

Abstract

The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.

Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

“…Previous studies by our research group have shown that mechanical/orthodontic forces can regulate the bacteria-induced levels of some proinflammatory and anti-apoptotic molecules [17][18][19]. The synthesis of some of these molecules during periodontal inflammation is further enhanced by mechanical/orthodontic forces, whereas other molecules tend to be downregulated [17][18][19]. Overall, these studies show that mechanical/orthodontic forces can influence the host immunoinflammatory response to periodontal bacteria.…”

“…The animal and in vitro experiments further showed that mechanical or orthodontic forces affect the bacteria-induced levels of such molecules very differently. For example, mechanical forces inhibited the stimulatory effect of F. nucleatum on CXCL1, CCL2, CCL5, SOD2, and BIRC3, whereas the F. nucleatum-induced upregulation of CXCL5, CXCL8, and CXCL10 was enhanced [17][18][19]. Overall, these previous studies demonstrated that mechanical/orthodontic forces can influence the host immunoinflammatory response to periodontal bacteria.…”

“…In our previous studies, we detected increased levels of numerous other chemokines in human and rat gingiva from sites with periodontal inflammation compared to periodontally healthy sites [18,19]. Anti-and pro-apoptotic molecules were also elevated at sites of periodontal inflammation [17]. The animal and in vitro experiments further showed that mechanical or orthodontic forces affect the bacteria-induced levels of such molecules very differently.…”

“…Bacteria were suspended in phosphate-buffered saline (OD 660 =1.0, equivalent to 1.2×10 9 bacterial cells/mL) and subjected to ultrasonic sonication twice (160 W for 15 min). To simulate orthodontic tooth movement in vitro, periodontal fibroblasts were subjected to constant tensile strain (CTS) for up to 2 days using an established cell stretching device, as in previous studies [17][18][19]. In addition, cells were also exposed to F. nucleatum and CTS simultaneously.…”

“…F. nucleatum plays a significant etiopathogenetic role in gingivitis and periodontitis [12][13][14][15][16]. Previous studies by our research group have shown that mechanical/orthodontic forces can regulate the bacteria-induced levels of some proinflammatory and anti-apoptotic molecules [17][18][19]. The synthesis of some of these molecules during periodontal inflammation is further enhanced by mechanical/orthodontic forces, whereas other molecules tend to be downregulated [17][18][19].…”