Epigenetic factors associated with peri-implantitis: a review

Abstract

Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue. Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence, influencing diverse physiological activities, including immune response, inflammation, and bone metabolism. Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition. However, the impact of these factors on peri-implantitis remains inconclusive. To address this gap, we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis, specifically focusing on DNA methylation and microRNAs (miRNAs or miRs). We searched for relevant literature on PubMed, Web of Science, Scopus, and Google Scholar with keywords including "epigenetics," "peri-implantitis," "DNA methylation," and "microRNA." DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants. Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis. In addition, we assessed the potential application of DNA methylation and miRNAs in the prevention, diagnosis, and treatment of peri-implantitis, aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition. These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.

Keywords: DNA methylation; Epigenetics; MicroRNA; Peri-implantitis.

Fig. 1. Relationship between epigenetics and peri-implantitis. Peri-implantitis is closely associated with microbial infections, host immune responses, and the tissue environment surrounding the implant. Epigenetic alterations in peri-implantitis may serve as a crucial link between environmental factors and host immune responses. Many investigators have begun to explore the use of epigenetically modified implant surfaces and epigenetic drugs for the diagnosis, prevention, and treatment of peri-implantitis (Created with bioRender.com). miRNA: microRNA; mRNA: messenger RNA; Pri-: primary; Pre-: precursor; RISC: RNA-induced silencing complex; DNMT: DNA methyltransferase.

Fig. 2. Relationships of microRNAs (miRNAs) specifically expressed in peri-implantitis with bone remodeling. When tissues are exposed to bacterial lipopolysaccharide (LPS), the expression of miRNAs can increase the sensitivity of Toll-like receptors (TLRs), target the nuclear factor-κB (NF-κB) signaling pathway, or regulate mitogen-activated protein kinase (MAPK)-mediated endotoxin tolerance. miR-21: Inhibition of Dickkopf-1 (DKK1), Sma- and Mad-related protein 7 (Smad7), Sprouty2 (SPRY2), and phosphatase and tensin homolog (PTEN) by miR-21 leads to activation of the Wnt and Smad pathways, increasing osteogenesis; inhibition of osteoprotegerin (OPG) by miR-21 leads to the activation of receptor activator of NF-κB (RANK) ligand (RANKL), increasing osteoclastogenesis. miR-150-5p: Inhibition of matrix metalloproteinase 14 (MMP14) by miR-150-5p leads to activation of the Wnt pathway, increasing osteogenesis. miR-27a: Inhibition of DKK2 and secreted frizzled-related protein 1 (SFRP1) by miR-27a leads to activation of the Wnt pathway, increasing osteogenesis. miR-146a: Inhibition of tumor necrosis factor-α (TNF-α) by miR-146a leads to suppression of osteoclastogenesis. miR-145: Inhibition of semaphorin 3A (SEMA3A) by miR-145 leads to suppression of osteogenesis (Created with bioRender.com). AKT: protein kinase B; BMP: bone morphogenetic protein; GSK-3β: glycogen synthase kinase-3β; JAK: Janus kinase; Lrp5/6: low-density lipoprotein receptor-related protein 5/6; PI3K: phosphatidylinositol 3-kinase; RUNX2: Runt-related transcription factor 2; STAT: signal transducer and activator of transcription; TRAF6: tumor necrosis factor (TNF) receptor-associated factor 6; Wnt: wingless/integrated.