The Role of Alcohol, LPS Toxicity, and ALDH2 in Dental Bony Defects

Abstract

It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 mutation in conjunction with periodontal Porphyromonas gingivalis bacterial infection and alcohol drinking had an inhibitory effect on osteoblasts and bone regeneration. We examined the prospective association of ALDH2 activity with the proliferation and mineralization potential of human osteoblasts in vitro. The ALDH2 knockdown experiments showed that the ALDH2 knockdown osteoblasts lost their proliferation and mineralization capability. To mimic dental bacterial infection, we compared the dental bony defects in wild-type mice and ALDH2*2 knockin mice after injection with purified lipopolysaccharides (LPS), derived from P. gingivalis which is a bacterial species known to cause periodontitis. Micro-computed tomography (micro-CT) scan results indicated that bone regeneration was significantly affected in the ALDH2*2 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH2*2 knockin mutant mice had decreased osteoblast growth and more dental bone loss in the upper left jaw region after LPS injection. In conclusion, these results indicated that the ALDH2*2 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.

Chronic periodontitis induces the proliferation of pancreatic β‐cells to cause hyperinsulinemia in a rat model

“…[32][33][34][35] In our study, CP was induced by injecting the classic toxin, P. gingivalis-LPS, into the periodontal pocket. As for the Con group, PBS, [24][25][26] saline solution, 36 or endotoxin-free water 37 as the solvent of LPS could be used in the previous similar studies.…”

Aldehydes, Aldehyde Metabolism, and the ALDH2 Consortium

“…In this study, a high-resolution accurate mass data-dependent constant neutral loss mass spectroscopy methodology was developed that identified two previously unreported acetaldehyde-induced DNA adducts ( N 6 -ethyldeoxyadenosine and N 4 -ethyldeoxycytidine), in addition to twenty putative acetaldehyde-DNA adducts. In a separate study, Tsai et al examined in rodents how the ALDH2*2 genetic variant can impact bone loss with dental bacteria (lipopolysaccharides derived from Polyphyromonas gingivalis ) concomitantly with alcohol [ 13 ]. By quantifying the proliferation and mineralization of human osteoblasts in vitro, it was observed that ALDH2 knockdown-transfected osteoblasts grew more slowly (about 5% calcification at day 14), compared to the control-transfected osteoblasts.…”

Effect of Lipopolysaccharide-Induced Apical Periodontitis in Diabetes Mellitus Rats on Periapical Inflammation

“…5 This condition damages the tissues in the periapical area and involves systemic host factors including the production of inflammatory mediators. 6 Inflammatory mediators are closely related to involved microorganisms. One of many microorganisms responsible for periodontitis, periapical lesions, and endodontic treatment failures is Porphyromonas gingivalis .…”