Mangiferin alleviates experimental peri-implantitis via suppressing interleukin-6 production and Toll-like receptor 2 signaling pathway

Abstract

Background: TLR2 (Toll-like receptor 2) signaling and its downstream proinflammatory cytokines are considered to be important in the progression of peri-implantitis. A natural medicine, mangiferin has exhibited modulatory effect on TLR2 signaling and anti-inflammatory effects on different diseases. The objective of the present study is to investigate the effect of mangiferin on peri-implantitis and the potential mechanisms by administering this drug to an experimental peri-implantitis mouse model. Methods: Maxillary left first, second, and third molars of mice were extracted, and dental implants were placed in the region of the maxillary left second molars. Then, peri-implantitis was induced by tying ligatures around implants, and mangiferin was given orally to the mice. After 6-week mangiferin treatment, bone loss around the implants was detected using micro-computerized tomography (micro-CT). Alveolar bone and inflammatory infiltrate in peri-implant tissues were examined using hematoxylin and eosin (H&E) staining. Production of interleukin-6 (IL6), a TLR2 downstream proinflammatory cytokine, in the tissue surrounding implants was measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. IL6 protein expression and TLR2 signaling pathway activation in peri-implant tissues were detected using western blot analysis.Results: Micro-CT demonstrated reduced bone loss in peri-implantitis upon mangiferin administration. Additionally, H&E staining showed more alveolar bone and less inflammatory infiltrate in peri-implant tissues after mangiferin application. Moreover, qRT-PCR analysis demonstrated lower levels of IL6 gene expression, and western blot analysis showed decreased protein expression of IL6 and TLR2, and suppressed phosphorylation of TLR2 downstream nuclear factor-κB, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase after mangiferin treatment.Conclusions: These results suggest the suppressive effect of mangiferin on bone damage and inflammatory infiltrate in peri-implantitis. These therapeutic effects may be associated with inhibited IL6 production and reduced TLR2 signaling activation in peri-implant tissues.

N‑acetyl cysteine inhibits the lipopolysaccharide‑induced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP/NLRP3/IL‑1β signaling pathway

“…A number of studies have demonstrated that LPS-induced overproduction of IL-1β, il-6 and TnF-α contributes to the majority of inflammatory responses that are involved in the pathogenesis of inflammatory-stimulated oral bone diseases, including periodontitis (35), peri-implantitis (36) and apical periodontitis (37). By contrast, our previous studies identified that NAC inhibited LPS-mediated synthesis of IL-1β, il-6 and TnF-α (10,26).…”

Levels of SERPIN family proteins in peri‐implant crevicular fluid in patients with peri‐implantitis

“…Therefore, the initiation of peri‐implant mucositis's early diagnosis and treatment must be essential for peri‐implantitis prevention 17,18 . Previous studies have demonstrated that nearly 45% of implant sites and closely 55% of implant patients could represent peri‐implantitis disease, 6 which mostly shows damage in peri‐implant tissue, specifically destruction of alveolar bone around implants and absolute inflammatory response, leads to loss of implant if left it without any treatment 19 …”

“…17,18 Previous studies have demonstrated that nearly 45% of implant sites and closely 55% of implant patients could represent peri-implantitis disease, 6 which mostly shows damage in peri-implant tissue, specifically destruction of alveolar bone around implants and absolute inflammatory response, leads to loss of implant if left it without any treatment. 19 SERPINBs are crucial in the function of the immune system and inflammation, and the production of mucous. 20 Previous researches 23 Besides, SERPINB5 had been reported in breast and prostate cancer as a tumor suppressor gene to inhibit metastasis.…”

Identification of Potential Genetic Biomarkers and Target Genes of Peri-Implantitis Using Bioinformatics Tools

“…Although the underlying pathogenic mechanisms of peri-implantitis remain unclear, the excessive inflammatory response due to the microbial biofilms on implants and their toxins is believed to play an important role in the occurrence of peri-implantitis [ 5 , 6 ]. Therefore, the immune-inflammatory response elicited by the bacterial biofilm may be responsible for the gingival recession and alveolar bone loss associated with peri-implantitis.…”