The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts

Gao, Hui; Sun, Tianyong; Yang, Fanghong; Yuan, Jiakan; Yang, Mei; Kang, Wenyan; Tang, Di; Zhang, Jun; Feng, Qiang

doi:10.3389/fcell.2020.00807

Cited by 12 publications

(14 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So far, little is known about the role of BIRC3 in oral physiology and pathophysiology. BIRC3 was recently identified as one of many other regulated genes in F. nucleatum -stimulated rat osteoblasts by whole-transcriptome analyses [ 14 ]. Moreover, periodontal ligament (PDL) cells have been shown to produce BIRC3, which could be increased by high tensile forces [ 15 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…The superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3), also known as cIAP2, are two molecules that seem to be involved in the actions of microbial and mechanical signals on periodontal cells and tissues [ 12 , 13 , 14 , 15 ]. SOD2 can convert toxic superoxide into hydrogen peroxide and diatomic oxygen.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Rath-Deschner

Nogueira

Memmert

et al. 2021

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Rath-Deschner

Nogueira

Memmert

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that absorption of the alveolar bone by Porphyromonas gingivalis, Campylobacter rectus, and Fusobacterium nucleatum is mediated by arachidonic acid metabolites, such as prostaglandins (Gao et al, 2020). Fusobacterium nucleatum can act on osteoblasts, which is reflected in the reduced expression of osteogenic genes and proteins (Reis et al, 2016), inhibition of cell differentiation, formation of mineralized nodules, and increased production of pro-inflammatory factors (Gao et al, 2020) (Figure 1).…”

Section: Fusobacterium Nucleatummentioning

confidence: 94%

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Xu-tao

Wan

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Chronic periapical periodontitis (CAP) is a typical oral disease in which periodontal inflammation caused by an odontogenic infection eventually leads to bone loss. Uncontrolled infections often lead to extensive bone loss around the root tip, which ultimately leads to tooth loss. The main clinical issue in the treatment of periapical periodontitis is the repair of jawbone defects, and infection control is the first priority. However, the oral cavity is an open environment, and the distribution of microorganisms through the mouth in jawbone defects is inevitable. The subversion of host cell metabolism by oral microorganisms initiates disease. The presence of microorganisms stimulates a series of immune responses, which in turn stimulates bone healing. Given the above background, we intended to examine the paradoxes and connections between microorganisms and jaw defect repair in anticipation of new ideas for jaw defect repair. To this end, we reviewed the microbial factors, human signaling pathways, immune cells, and cytokines involved in the development of CAP, as well as concentrated growth factor (CGF) and stem cells in bone defect repair, with the aim of understanding the impact of microbial factors on host cell metabolism to inform the etiology and clinical management of CAP.

show abstract

“…Amyloid-like FadA was shown to induce periodontal bone loss and promote colorectal cancer (CRC) progression in mice ( Meng et al, 2021 ). Other research teams also found that F. nucleatum could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts or Gingiva-Derived Mesenchymal Stem Cells ( Kang et al, 2019a ; Gao et al, 2020 ). More experiments are needed to support this conclusion in the future.…”

Section: Discussionmentioning

confidence: 98%

Outer Membrane Vesicles From Fusobacterium nucleatum Switch M0-Like Macrophages Toward the M1 Phenotype to Destroy Periodontal Tissues in Mice

et al. 2022

View full text Add to dashboard Cite

Periodontitis is a chronic inflammatory oral disease that affects nearly 50% of all adults. Fusobacterium nucleatum (F. nucleatum) is known to be involved in the formation and development of periodontitis. Outer membrane vesicles (OMVs) harboring toxic bacterial components are continuously released during F. nucleatum growth and regulate the extent of the inflammatory response by controlling the functions of immune and non-immune cells in tissues. Macrophages are important immune cells in periodontal tissue that resist pathogen invasion and play an important role in the pathophysiological process of periodontitis. However, the role of the interaction between F. nucleatum OMVs and macrophages in the occurrence and development of periodontitis has not been studied. The purpose of this study was to clarify the effect of F. nucleatum OMVs on the polarization of macrophages and the roles of this specific polarization and F. nucleatum OMVs in the pathophysiology of periodontitis. The periodontitis model was established by inducing ligation in C57BL/6 mice as previously described. Micro-CT, RT-qPCR, hematoxylin-eosin (H&E) and tartrate acid phosphatase (TRAP) staining assays were performed to analyze the periodontal tissue, alveolar bone loss, number of osteoclasts and expression of inflammatory factors in gingival tissue. The changes in the state and cytokine secretion of bone marrow-derived macrophages (BMDMs) stimulated by F. nucleatum OMVs were observed in vivo by confocal microscopy, flow cytometry, Western blot and ELISA. Mouse gingival fibroblasts (MGFs) were isolated and then cocultured with macrophages. The effects of F. nucleatum OMVs on the proliferation and apoptosis of MGFs were analyzed by flow cytometry and lactate dehydrogenase (LDH) assays. The periodontitis symptoms of mice in the F. nucleatum OMVs + ligation group were more serious than those of mice in the simple ligation group, with more osteoclasts and more inflammatory factors (IL-1β, IL-6, and TNF-α) being observed in their gingival tissues. M0 macrophages transformed into M1 macrophages after the stimulation of BMDMs with F. nucleatum OMVs, and the M1 macrophages then released more inflammatory cytokines. Analysis of the coculture model showed that the MGF apoptosis and LDH release in the inflammatory environment were increased by F. nucleatum OMV treatment. In conclusion, F. nucleatum OMVs were shown to aggravate periodontitis, alveolar bone loss and the number of osteoclasts in an animal model of periodontitis. F. nucleatum OMVs promoted the polarization of macrophages toward the proinflammatory M1 phenotype, and the inflammatory environment further aggravated the toxicity of F. nucleatum OMVs on MGFs. These results suggest that M1 macrophages and F. nucleatum OMVs play roles in the occurrence and development of periodontitis.

show abstract

The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts

Cited by 12 publications

References 66 publications

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

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

Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis

Outer Membrane Vesicles From Fusobacterium nucleatum Switch M0-Like Macrophages Toward the M1 Phenotype to Destroy Periodontal Tissues in Mice

Contact Info

Product

Resources

About