The Role of Lactic Acid on Wound Healing, Cell Growth, Cell Cycle Kinetics, and Gene Expression of Cultured Junctional Epithelium Cells in the Pathophysiology of Periodontal Disease

Abstract

Lactic acid (LA) is short-chain fatty acid, such as butyric acid and propionic acid, that is produced as a metabolite of lactic acid bacteria, including periodontopathic bacteria. These short-chain fatty acids have positive effects on human health but can also have negative effects, such as the promotion of periodontal disease (PD), which is caused by periodontal pathogens present in the gingival sulcus. PD is characterized by apical migration of junctional epithelium, deepening of pockets, and alveolar bone loss. Thus, the junctional epithelial cells that form the bottom of the gingival sulcus are extremely important in investigating the pathophysiology of PD. The aim of this study was to investigate the effect of LA on wound healing, cell growth, cell cycle kinetics, and gene expression of cultured junctional epithelium cells. The results showed that stimulation with 10 mM LA slowed wound healing of the junctional epithelial cell layer and arrested the cell cycle in the G0/G1 (early cell cycle) phase, thereby inhibiting cell growth. However, cell destruction was not observed. LA also enhanced mRNA expression of integrin α5, interleukin (IL)-6, IL-8, intercellular adhesion molecule-1, and receptor activator of nuclear factor kappa-B ligand. The results of this study suggest that stimulation of junctional epithelial cells with high concentrations of LA could exacerbate PD, similarly to butyric acid and propionic acid.

Ultrasound-Assisted Extraction of Antioxidants from Melastoma malabathricum Linn.: Modeling and Optimization Using Box–Behnken Design

“…Several studies also reported its ability to prevent atherosclerotic lesions [ 37 ], skin problems [ 38 ], and cancer [ 39 ]. Lactic acid (LA), identified as another major compound present in the extract, is essentially a short-chain fatty acid, such as butyric acid and propionic acid, produced as a metabolite of lactic acid bacteria, including periodontopathic bacteria [ 40 ]. These short-chain fatty acids have been cited to have positive effects on human health.…”

Study on the effect of protein lysine lactylation modification in macrophages on inhibiting periodontitis in rats

“…Studies have shown that lactate inhibited the expression of alkaline phosphatase (ALP) through G protein‐coupled receptor 81 α subunit signal and reduced autophagy through the MCT1‐mTOR signal pathway, thus inhibiting the osteogenic differentiation of human periodontal ligament stem cells 11 . Importantly, it has been demonstrated that lactate in high concentration increased the mRNA expression of inflammatory factors such as integrin α5, IL‐6, IL‐8, intercellular adhesion molecule‐1, and receptor activator of nuclear factor κB ligand and stimulated junctional epithelial cells, thus aggravating PD 9 …”

“…The lactate in PD originates from bacteria and tissue metabolism in the subgingival plaque, 9 resulting in higher lactate levels in the gingival crevicular fluid of patients with PD than in healthy individuals. 10 In this study, we observed substantially higher lactate content in the clinical periodontal tissues when compared to the levels in normal tissue.…”

“…11 Importantly, it has been demonstrated that lactate in high concentration increased the mRNA expression of inflammatory factors such as integrin α5, IL-6, IL-8, intercellular adhesion molecule-1, and receptor activator of nuclear factor κB ligand and stimulated junctional epithelial cells, thus aggravating PD. 9 Lactate, the final product of aerobic glycolysis, has long been considered the metabolic waste of glycolysis in the cell and as not being conducive to the healing of PD. However, recent studies have demonstrated its important role in gene transcription, 12 cancer development, 13 immune cell function, 14 and stem cell maintenance.…”