Triggering receptor expressed on myeloid cells in the pathogenesis of periodontitis: potential novel treatment strategies

Abstract

Introduction Periodontal diseases are polymicrobial inflammatory disorders of the tissue, ligament, and bone structures supporting teeth. Periodontitis (inflammation with corresponding loss of attachment) affects 40–50% of adults. Recently, members of the Triggering Receptor on Myeloid Cell (TREM) family have been studied to determine their relationship to these diseases. Areas covered TREM-1 is a receptor expressed on the surface of PMNs, monocytes, macrophages, dendritic cells, vascular smooth muscle cells, and keratinocytes upregulated in the presence of periodontal inflammation. TREM-1 expression can be upregulated by oral bacterium Porphyromonas gingivalis that can be abrogated by a sub-antimicrobial dose of doxycycline. When cleaved from the cell surface, a soluble form of TREM-1 (sTREM-1) can be used as a biomarker of inflammation and might also provide a link between oral and systemic inflammation. While less understood, TREM-2 has a role in osteoclastogenesis which could contribute to the alveolar bone destruction seen in more advanced periodontitis. Expert Commentary Additional studies to simulate biofilm microenvironment in TREM research are warranted. Longitudinal studies determining TREM-1, sTREM-1, and TREM-2 levels in tissues over time and progression of periodontal diseases would provide valuable information in the role of TREM receptors as indicators of or contributors to the disease process.

Blood and Salivary Inflammatory Biomarkers Profile in Patients with Chronic Kidney Disease and Periodontal Disease: A Systematic Review

“…Romandini et al [ 54 ] concluded that periodontitis influences WBC count by an increase in systemic inflammation, and Arai et al [ 55 ] concluded that WBC is independently associated with CKD progression. These two articles that studied WBC showed high levels in patients with periodontitis, suggesting a systemic inflammation caused by periodontitis [ 37 , 46 , 56 , 57 ].…”

Periodontal Inflammation and Systemic Diseases: An Overview

“…Host modulation therapies (Bartold and Van Dyke, 2017 ; Hajishengallis et al, 2020 ) combining anti-inflammatory and antioxidant agents have shown promising effects to treat PD in clinical trials (Sulijaya et al, 2019 ). Other biologics used as novel therapeutic strategies involve molecules able to trigger myeloid cell receptors (Rudick et al, 2017 ) since these cells are known players in pathogenic inflammation (Peddis et al, 2019 ). The novel anti-inflammatory drug tetramethylpyrazine has been recently found to reduce inflammation levels as well as LPS-mediated apoptosis in human periodontal ligament cells by a mechanism involving the downregulation of the small non-coding RNA miR-302b (Duan et al, 2020 ).…”

Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis

“…Periodontitis is a biofilm-driven chronic inflammatory disease during which a dysbiotic periodontal microbiota induces adverse immune responses that further lead to the destruction of tooth-supporting tissues and ultimately tooth loss [19][20][21] . Several studies have investigated TREM-1 and PGLYRP1 in the context of periodontal disease and recently TREM-1 has been suggested as a candidate marker for new treatment strategies against periodontal diseases 22,23 . Elevated TREM-1 levels were observed in saliva, serum and gingival crevicular fluids (GCF) in patients with periodontitis, and TREM-1 serum and saliva levels correlated positively [24][25][26][27] .…”