Notch down‐regulation and inflammatory cytokines and RANKL overexpression involvement in peri‐implant mucositis and peri‐implantitis: A cross‐sectional study

• Published in: Clinical oral implants research 2021-12, Vol.32 (12), p.1496-1505
• Main Authors: Milinkovic, Iva, Djinic Krasavcevic, Ana, Nikolic, Nadja, Aleksic, Zoran, Carkic, Jelena, Jezdic, Marija, Jankovic, Sasha, Milasin, Jelena
• Format: Article
• Language: English
• Subjects: Biomedical materials; Bone remodeling; Bone resorption; Cross-Sectional Studies; Cytokines; Cytokines - metabolism; Dental Implants; Down-Regulation; Enzyme-linked immunosorbent assay; Humans; Inflammation; Modulators; Mucositis; notch signaling; Notch1 protein; Osteolysis; Osteoprotegerin; Parameters; Peri-Implantitis; peri‐implant diseases; peri‐implant mucositis; Plaque index; Polyimide resins; Polymerase chain reaction; Proteins; Quantitation; RNA-directed DNA polymerase; Signal transduction; TRANCE protein; Transplants & implants; Tumor necrosis factor
• ISSN: 0905-7161; 1600-0501
• DOI: 10.1111/clr.13850

Objectives Notch signaling pathway, known to influence bone resorption in several oral diseases, has not been analyzed in peri‐implantitis yet. Therefore, the aims of the present study were to determine the levels of Notch cascade, bone remodeling mediators, and pro‐inflammatory cytokines, in conjunction with clinical parameters, in subjects with peri‐implant mucositis and peri‐implantitis. Material and methods Clinical parameters: peri‐implant probing depth, bleeding on probing, suppuration on probing, and plaque index (PI) were recorded. Samples were collected from 130 participants, divided into peri‐implantitis (PI), peri‐implant mucositis (PM), and healthy implants (HI) group. Relative expression levels (REL) of Notch 1, Notch 2, Jagged 1, Hes 1, Hey 1, TNF‐α, IL‐17, IL‐1β, IL‐6, RANKL, and OPG mRNA were determined by reverse transcriptase‐real‐time polymerase chain reaction. Quantitation of Notch 1, Il‐17, and IL‐6 proteins was performed using ELISA assays. Results All clinical parameters were significantly higher in PI compared to HI. Significant decrease of Notch 1, and higher REL of Hey 1, IL‐1β, IL‐6, and RANKL were found in PI compared to HI. PM showed significant increase of IL‐1β REL in comparison with HI. In PI versus PM, significantly higher REL was found for Hey 1, TNF‐α, IL‐17, IL‐1β, IL‐6, and RANKL. Additionally, higher protein concentrations of IL‐6 and IL‐17 were detected in PI versus PM and versus HI group. Conclusion The combined effect of Notch 1 down‐regulation and elevated expression of some key inflammation modulators might result in osteoclast activity increase and subsequent osteolysis in peri‐implantitis.