Semaphorin 3A protects against alveolar bone loss during orthodontic tooth movement in mice with periodontitis

Abstract

Objective This study investigated the effect of local semaphorin 3A (Sema3A) administration on alveolar bone loss during OTM in a mouse model of periodontitis. Background Orthodontic tooth movement (OTM) for patients with periodontal disease is known to increase the risk of exacerbating alveolar bone loss due to inflammation of the periodontal tissue. However, its mechanism of action and prevention remains unclear. Methods Mice (male 7–8 weeks old, C57BL/6J, n = 12) were divided into six groups: untreated group (control), without OTM and recovered from induced periodontitis (RP), with OTM and administered PBS or Sema3A to the gingiva after induced periodontitis (VehPO, SemaPO), with OTM and administered PBS or Sema3A to the gingiva without periodontitis induction (VehNO, SemaNO). Samples were collected on 14 days, and bone loss, histological analysis, cytokine production level, and tooth movement were assessed. Cultured human periodontal ligament (hPDL) cells were stimulated with lipopolysaccharide (LPS) and compressive force (CF), and mRNA expression levels of Sema3A and its receptors were analyzed. Results The bone loss was significantly lower in the SemaPO group than in the VehPO group. The number of TRAP‐positive cells in the SemaPO group was significantly lower than that in the VehPO group and was at the same level as that in the control group. The receptor activator of nuclear factor (NF)‐kB‐ligand/osteoprotegerin (RANKL/OPG) ratio and the levels of proinflammatory cytokines, including interleukin (IL)‐1β, IL‐6, IL‐17, tumor necrosis factor (TNF)‐α, and interferon (IFN)‐γ, in the gingival tissues were significantly lower in the SemaPO group than in the VehPO group. Additionally, Sema3A mRNA expression in hPDL cells was significantly decreased by co‐stimulation with LPS and CF compared with that in the control group. Finally, the distance moved (dist.) and the mesial tipping angle (θ) was significantly smaller in the SemaPO group than in the VehPO group and was not significantly different from that of VehNO. Conclusion Pathological alveolar bone loss exacerbated by OTM in periodontitis might be prevented by local administration of Sema3A without inhibiting OTM.

The role of Semaphorin 3A in oral diseases

“…However, it is discovered that the Wnt pathway functions as an osteogenesis inhibitor in an LPS‐induced inflammatory environment, and SEMA3A can attenuate this inhibitory effect (Sun et al, 2021). In a mouse model of periodontitis, SEMA3A administration during orthodontic tooth movement significantly decreased the levels of cytokines IL‐1β, IL‐6, IL‐7, TNF‐α, and IFN‐γ, protecting against alveolar bone loss (Satomi et al, 2022). The oxygen content in the periodontal microenvironment also influences the periodontitis occurrence and progression (Li et al, 2012; Takedachi et al, 2017).…”

“…Reducing pro-inflammation cytokines in mice with orthodontic treatment (Satomi et al, 2022) Regulating the polarization of M1/M2 macrophages in LPSinduced periodontitis in mice (Tian et al, 2023) Reducing CD4(+) T cell activation in gingival tissue (Catalano, 2010;Okui et al, 2012) Alveolar bone remodeling Promoting the osteogenic differentiation in rGMSCs and rBMSCs (Sun et al, 2021;Tian et al, 2019) Attenuating bone loss by downregulating the level of pro-inflammation cytokines in mice with orthodontic treatment (Satomi et al, 2022) Weakening osteogenesis inhibition caused by the Wnt pathway in rBMSCs and hypoxia in PDLSCs (Chang et al, 2022;Sun et al, 2021) Pulpitis Apical periodontitis…”

“…Studies have revealed that local gingival administration of SEMA3A can reduce cytokines like IFN‐γ and IL‐2 during orthodontic treatment in periodontitis mice (Satomi et al, 2022). In addition, recent study recent research has shown that SEMA3A can also achieve anti‐inflammatory effects by regulating the polarization of M1/M2 macrophages in periodontitis (Tian et al, 2023).…”