Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 100, Taiwan.
Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan.
Biomolecules. 2021 Apr 28;11(5):651. doi: 10.3390/biom11050651.
It is estimated that 560 million people carry an East Asian-specific ALDH22 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH22 mutation in conjunction with periodontal 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 ALDH22 knockin mice after injection with purified lipopolysaccharides (LPS), derived from 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 ALDH22 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH22 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 ALDH22 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.
据估计，有 5.6 亿人携带东亚特有的 ALDH22 显性负突变，导致酶失活。这种常见的 ALDH2 多态性与骨质疏松症有显著关联。我们假设 ALDH22 突变与牙周细菌感染和饮酒结合在一起，对成骨细胞和骨再生有抑制作用。我们研究了 ALDH2 活性与体外人成骨细胞增殖和矿化潜能的前瞻性关联。ALDH2 敲低实验表明，ALDH2 敲低的成骨细胞失去了增殖和矿化能力。为了模拟牙细菌感染，我们比较了野生型小鼠和 ALDH22 敲入型小鼠在注射纯化脂多糖（LPS）后的牙骨缺损情况，LPS 来源于一种已知会引起牙周炎的细菌物种。微计算机断层扫描（micro-CT）扫描结果表明，ALDH22 敲入型小鼠的骨再生受到明显影响，在 LPS 注射后，牙骨缺损比野生型小鼠多 20%左右。此外，在 LPS 注射后，ALDH22 敲入突变型小鼠的成骨细胞生长减少，左上颚区域的牙骨丢失更多。总之，这些结果表明，ALDH22 突变与饮酒和慢性暴露于牙细菌衍生的毒素会增加牙骨丢失的风险。
