Effect of advanced glycation end products on periodontal tissue

Advanced glycation end products, AGEs is produced in large quantities in diabetic patients, and its production is irreversible, and it will accumulate gradually over time. Therefore, the content of AGEs in tissues can represent the degree and time of diabetes development. In addition, AGEs is closely related to the occurrence and development of diabetes and various complications.

Periodontitis is the sixth complication of diabetes mellitus. Periodontitis in diabetic patients develops rapidly, and the disease is serious and the treatment is more difficult. The two-way relationship between them has been supported by a lot of research. In recent years, studies have shown that AGEs plays an important role in the occurrence and development of periodontitis in diabetic patients. 

Ages is a kind of stable end products formed by non enzymatic reaction of free amino groups of biological macromolecules such as protein, nucleic acid and lipid with aldehyde or ketone groups of reducing sugar. This process is called glycosylation reaction, which is stable and irreversible. Fluorescence spectroscopy and enzyme-linked immunosorbent assay are generally used to determine the concentration.

According to the current research, we found that ages damage to the body mainly through three mechanisms: ① ages on islets β Cells have direct toxic effects. ② The cross-linking of ages with protein leads to the change of protein structure and function. ③ Ages binds to the receptor to activate the signaling pathway.

At present, there are many ages receptors, among which the research on the receptor of advanced glycosylated end product (RAGE) is more in-depth. Rage is expressed on many cell surfaces, such as endothelial cells, fibroblasts, smooth muscle cells, etc. Ages can activate ERK, p38, JNK and PCK after binding with rage on the cell surface, which can induce many oxidative stress or inflammatory reactions. 

In previous studies, the levels of AGEs in normal or inflammatory periodontal tissues of diabetic rats were higher than those in non-diabetic rats, and AGEs levels in gingival tissues were higher in diabetic periodontitis patients. The accumulation of AGEs in periodontal tissue will aggravate periodontal inflammation, and in a diabetic Ganges RIver monkey experiment, periodontal inflammation can also raise the level of serum AGEs. In addition, inflammatory periodontal tissue has high RAGE content, making it more sensitive to AGEs. The influence of ages on periodontal tissue includes alveolar bone and soft tissue. In recent years, the research focuses on cell level 

Ages can inhibit the proliferation and osteogenic differentiation of periodontal ligament stem cells, and stimulate the expression of inflammatory factors in a concentration and time-dependent manner. Ages may inhibit the expression of cylind1 by activating HSG, which makes the cells stagnate in G0 / G1 phase and finally inhibits the proliferation of cells. The osteogenic differentiation ability of stem cells may be mediated by

The ages / rage / ROS pathway or the activation of Wnt classical pathway were inhibited, and could promote stem cell apoptosis. Ages can also promote adipogenic differentiation of human periodontal ligament stem cells and adipose tissue. The irreversible damage of AGEs to periodontal ligament stem cells explains the serious and serious failure of periodontal inflammation in diabetic patients.

Li Found that ages can induce apoptosis of periodontal fibroblasts through rage pathway. It has been reported that ages can increase the number of autophagosomes in periodontal ligament fibroblasts and induce autophagy. Ages can also pass ages / rage / NF- κ Pathway B inhibited the synthesis of type I and type II collagen and increased the expression of matrix metalloproteinase-1.

The AGEs content in gums increased under diabetes and AGEs was RAGE, MAPK and NF-. κ B signaling pathway increases the expression of IL-6 and Lcn2 in oral epithelial cells. The secretion of Lcn2 can affect the pathological changes of periodontal tissue. At present, there are few studies on the effects of ages on gingival epithelial cells, and the specific effects still need to be explored. 

Osteoblasts can regulate bone metabolism by regulating the formation of osteoblasts and osteoclasts. Therefore, osteoblasts are also known as "commander cells" of bone remodeling. Some experiments have proved that ages can not only directly induce osteocyte apoptosis, but also inhibit bone resorption by reducing the expression of osteoclast differentiation factor RANKL. Although this process inhibits bone resorption, it also inhibits bone metabolism, The final result will lead to decreased bone turnover rate, reduced bone turnover and degeneration of cortical bone in diabetic patients.

In addition to RANKL pathway, ages can also activate ERK1 / 2, p38 and STAT3 signaling pathways through rage, promote osteocyte apoptosis and release interleukin-6 (IL-6) and vascular endothelial growth factor-A (VEGF-A) to aggravate inflammatory response.

The number and function of osteoclasts are closely related to the strength of bone resorption. The effect of ages on osteoclasts is still controversial. Some studies have reported that ages can promote bone resorption, that is, high concentration of ages can promote osteoclasts bone resorption activity, increase the number and area of bone lacunae, but some reports have raised objections. For example, VALCOURT et al. Found that ages can inhibit bone resorption activity by affecting the fusion of osteoclasts. No matter which point of view clearly points out that ages has an impact on the function of osteoclasts, whether it promotes bone resorption or inhibits bone resorption, it affects bone remodeling and is unfavorable to bone metabolism.

Animal experiments show that ages can significantly reduce the mRNA expression of osteoblast related molecules (such as type I collagen, osteocalcin and osteoblast specific transcription factor Cbfa1), reduce the protein level of osteocalcin and increase IL-1 β The activity of alkaline phosphatase in osteoblasts was inhibited and the formation of bone nodules was reduced. 

Periodontitis in diabetics is developing rapidly and seriously and is difficult to control. Because of the limited use of antibiotics in the process of controlling blood sugar, the treatment of diabetic patients with periodontitis is extremely difficult. It is now known that the accumulation of AGEs in periodontal tissues of diabetic patients can aggravate periodontal tissue inflammation. The deepening of AGEs pathogenetic pathway in periodontal tissue is helpful not only to deepen our understanding of the disease, but also to find new therapeutic approaches.

 

Cindy