Journal of Prevention and Treatment for Stomatological Diseases ›› 2019, Vol. 27 ›› Issue (7): 428-434.doi: 10.12016/j.issn.2096-1456.2019.07.004

• Basic Study • Previous Articles     Next Articles

Expression of the receptor of advanced glycation end products in gingival tissue endothelial cells from type 2 diabetic rats with chronic periodontitis

Gang WANG1,Peng SUN2,Juan LI3,Shiguang HUANG3()   

  1. 1.Department of Conservative Dentistry, Affiliated Zhongshan Hospital, Sun Yat-sen University, Zhongshan 528404, China
    2.Second Clinical Medicine College of Jinan University, Oral Medicine Center of Shenzhen People’s Hospital, Shenzhen 518020, China;
    3.School of Stomatology, Jinan University, Guangzhou 510632, China
  • Received:2018-10-30 Revised:2019-04-26 Online:2019-07-20 Published:2019-07-24
  • Contact: Shiguang HUANG E-mail:thshg@126.com

RichHTML

11

PDF (PC)

43

Abstract:

Objective To evaluate the expression of the receptor for advanced glycation end products (RAGE) in gingival tissue endothelial cells from type 2 diabetic rats with chronic periodontitis and to explore the role of RAGE in the pathogenesis of diabetes in cases with chronic periodontitis. Methods Sixty 7-week-old female Wistar diabetic obese rats were randomly divided into two groups. Periodontitis was induced in 30 rats by silk ligation, and the other 30 rats were used as the control group in which the periodontal tissues were not treated. One week after periodontal ligation and inoculation, the periodontitis and control group rats were randomly divided into two subgroups; the first subgroup was fed a high-fat diet, and the second group was fed a low-fat diet. Thus, 15 rats per group were included in the high-fat diet periodontitis (HF/P), low-fat diet periodontitis (LF/P), high-fat diet periodontal health (HF/C), and low-fat diet periodontal health (LF/C) groups. Glucose tolerance tests were performed weekly to measure the fasting insulin and blood glucose levels and the insulin resistance index to verify successful construction of the rat diabetes model. After successful modeling of chronic periodontitis, the rats were sacrificed at the 13th week after measurement of the serum necrosis factor-α (TNF-α), interleukin-6 (IL-6) and leptin levels. The tooth periodontal tissues were prepared and sectioned to observe histological changes. Immunofluorescence double staining was used to detect the density of RAGE-positive endothelial cells in the gingival tissues of the four groups. Results The serum fasting blood glucose and insulin levels and insulin resistance index were significantly higher in the HF/P and HF/C groups than in the LF/P and LF/C groups (P < 0.01). The serum TNF-α and IL-6 levels were significantly higher in the HF/P and LF/P groups than in the HF/C and LF/C groups (P < 0.01). The serum leptin levels were significantly higher in the HF/P group than in the other three groups. The density of RAGE-positive endothelial cells was significantly higher in the HF/P and HF/C groups than in the LF/P (P=0.001) and LF/C groups (P=0.040). The density of RAGE-positive endothelial cells in the HF/P group was higher than that in the HF/C group (P=0.027). Conclusion Endothelial cells in type 2 diabetic rats with periodontitis have increased gingival tissue RAGE and serum leptin levels.

Key words: type 2 diabetes mellitus, periodontitis, receptor for advanced glycation end products, endothelial cells, high fat diet, hyperglycaemia, leptin

CLC Number: 

  • R781.4

Table 1

Changes in the blood glucose levels of the rats in the four groups $\bar{x}$ ± s, mmol/L"

大鼠 P C 平均值 F值/t值 P值
HF 75.753 ± 5.382 41.253 ± 2.902 58.503 ± 25.357 137.548 <0.001
LF 58.584 ± 3.452 38.821 ± 1.773 48.703 ± 19.867 121.672 <0.001
平均值 67.169 ± 15.372 40.037 ± 5.141 53.603 ± 22.683 142.5311） <0.0011）
F值/t值 119.436 6.973 133.6531） F = 157.9132）
P值 < 0.001 0.205 < 0.0011） P < 0.0012）

Table 2

Changes in the insulin levels of the rats in the four groups $\bar{x}$ ± s, μg/L"

大鼠 P C 平均值 F值/t值 P值
HF 38.583 ± 0.856 30.052 ± 0.623 34.223 ± 5.040 11.538 0.001
LF 21.351 ± 0.652 20.823 ± 0.774 21.231 ± 0.395 0.654 0.549
平均值 29.968 ± 9.950 25.485 ± 5.070 27.727 ± 7.694 126.7361） <0.0011）
F值/t值 116.215 23.654 93.7671） F = 132.9092）
P值 <0.001 0.001 <0.0011） P < 0.0012）

Table 3

Changes in the insulin resistance index of the rats in the four groups $\bar{x}$ ± s"

大鼠 P C 平均值 F/t值 P值
HF 5.902 ± 0.313 4.852 ± 0.231 5.376 ± 0.605 5.156 0.030
LF 3.234 ± 0.153 3.241 ± 0.184 3.240 ± 0.006 0.523 0.875
平均值 4.569 ± 1.537 4.047 ± 0.930 4.308 ± 1.209 16.2151） 0.0071）
F值/t值 53.245 13.854 63.3621） F = 33.5522）
P值 0.001 0.007 0.0011） P = 0.0032）

Table 4

Changes in TNF-α expression in the rats in the four groups $\bar{x}$ ± s, μg/L"

大鼠 P C 平均值 F值/t值 P值
HF 88.203 ± 6.821 40.122 ± 3.254 64.163 ± 39.651 174.548 <0.001
LF 61.614 ± 5.352 39.452 ± 5.103 50.533 ± 22.458 164.243 <0.001
平均值 74.909 ± 16.672 39.787 ± 6.341 57.348 ± 35.784 171.4321） <0.0011）
F值/t值 154.452 3.753 87.7241） F = 132.6092）
P值 <0.001 0.763 < 0.0011） P<0.0012）

Table 5

Changes in IL-6 expression in the rats in the four groups $\bar{x}$ ± s, μg/L"

大鼠 P C 平均值 F值/t值 P值
HF 28.553 ± 0.512 20.125 ± 0.255 24.343 ± 4.890 3.301 0.033
LF 4.256 ± 0.435 4.655 ± 0.147 4.457 ± 0.443 0.468 0.361
平均值 16.412 ± 14.046 12.377 ± 8.931 14.396 ± 11.108 15.2111） < 0.0011）
F值/t值 131.705 153.691 122.4981） F = 148.0592）
P值 <0.001 <0.001 <0.0011） P<0.0012）

Table 6

Changes in leptin expression in the rats in the four groups $\bar{x}$ ± s, μg/L"

大鼠 P C 平均值 F值/t值 P值
HF 18.632 ± 3.453 8.453 ± 2.094 13.543 ± 11.564 42.823 <0.001
LF 8.231 ± 3.153 6.243 ± 2.181 7.237 ± 4.873 3.421 0.187
平均值 13.432 ± 9.376 7.348 ± 2.368 10.390 ± 8.657 36.4321） <0.0011）
F值/t值 34.572 3.784 47.8651） F = 28.2152）
P值 < 0.001 0.156 < 0.0011） P < 0.0012）

Figure 1

HE-stained images showing histological changes in the periodontal tissues in each group bar = 5 μm"

Figure 2

CD31-RAGE double-positive endothelial cell infiltration as determined by double immunofluorescence staining in the 4 groups using laser scanning confocal microscopy bar = 50 μm."

"

大鼠 P C 平均值 F值/t值 P值
HF 165.702 ± 15.304 102.853 ± 10.007 134.080 ± 37.348 153.654 0.027
LF 53.352 ± 5.441 40.604 ± 5.771 46.890 ± 7.434 25.869 0.415
平均值 109.456 ± 64.887 71.459 ± 36.643 90.485 ± 52.854 529.0361） P<0.0011）
F值/t值 431.551 116.651 467.6701） F = 649.6122）
P值 0.001 0.040 0.0011） P < 0.0012）
[1] Winning L, Patterson CC, Neville CE , et al. Periodontitis and incident type 2 diabetes: a prospective cohort study[J]. J Clin Periodontol, 2017,44(3):266-274.
doi: 10.1111/jcpe.2017.44.issue-3
[2] Acharya AB, Thakur S, Muddapur MV , et al. Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus[J]. Diabetes Metab Syndr, 2017,11(4):277-278.
doi: 10.1016/j.dsx.2016.12.007
[3] Grover HS, Luthra S . Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease[J]. J Indian Soc Periodontol, 2013,17(3):292-301.
doi: 10.4103/0972-124X.115642
[4] Amir J, Waite M, Tobler J , et al. The role of hyperglycemia in mechanisms of exacerbated inflammatory responses within the oral cavity[J]. Cell Immunol, 2011,272:45-52.
doi: 10.1016/j.cellimm.2011.09.008
[5] Gennaro G, Claudino M, Cestari TM , et al. Green tea modulates cytokine expression in the periodontium and attenuates alveolar bone resorption in type 1 diabetic rats[J]. PLoS One, 2015,10(8):e0134784.
doi: 10.1371/journal.pone.0134784
[6] Wu CH, Huang HW, Lin JA , et al. Theproglycation effect of caffeic acid leads to the elevation of oxidative stress and inflammation in monocytes, macrophages and vascular endothelial cells[J]. J Nutr Biochem, 2011,22(6):585-594.
doi: 10.1016/j.jnutbio.2010.05.002
[7] Wu TL, Tsai CC, Wang YY , et al. The association between the RAGE G82S polymorphism, sRAGE and chronic periodontitis in Taiwanese individuals with and without diabetes[J]. J Periodontal Res, 2015,50(6):881-889.
doi: 10.1111/jre.2015.50.issue-6
[8] Chen XM, Lin JZ, Hu TT , et al. Galectin-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin beta1-RhoA-JNK signaling activation[J]. J Cell Physiol, 2019,234(7):10990-11000.
doi: 10.1002/jcp.v234.7
[9] Li J, Wang R, Huang SG . Immunomodulatory activity of interleukin-27 in human chronic periapical diseases[J]. Am J Transl Res, 2017,9(3):1460-1470.
[10] Huang S, Lu F, Zhang Z , et al. The role of psychologic stress-induced hypoxia-inducible factor-1α in rat experimental periodontitis[J]. J Periodontol, 2011,82(6):934-941.
doi: 10.1902/jop.2010.100610
[11] Luo S, Yang X, Wang D , et al. Periodontitis contributes to aberrant metabolism in type 2 diabetes mellitus rats by stimulating the expression of adipokines[J]. J Periodontal Res. 2016,51(4):453-461.
doi: 10.1111/jre.2016.51.issue-4
[12] Saito T, Shimazaki Y, Kiyohara Y , et al. Relationship between obesity, glucose tolerance, and periodontal disease in Japanese women: the Hisayama study[J]. J Periodontal Res, 2005,40(4):346-353.
doi: 10.1111/jre.2005.40.issue-4
[13] PankovIu A, Chekhranova MK, Karpova SK . The interconnections of molecular mechanisms of hormone actions and their role in pathogenesis of obesity, insulin resistance, and diabetes mellitus[J]. Vestn Ross Akad Med Nauk, 2008,3:28-36.
[14] Tsubokawa M, Sato S . In vitro analysis of human periodontal microvascular endothelial cells[J]. J Periodontol, 2014,85(8):1135-1142.
doi: 10.1902/jop.2013.130209
[15] Takeichi O, Hatori K, Kamimoto A , et al. Receptor for advanced glycation end products (RAGE)-expressing endothelial cells co-express AGE and S100 in human periapical granulomas[J]. J Dent, 2011,39(10):679-685.
doi: 10.1016/j.jdent.2011.07.010
[16] Katz J, Wallet S, Cha S . Periodontal disease and the oral-systemic connection: “is it all the RAGE”?[J] Quintessence Int, 2010,41(3):229-237.
[17] Schmidt AM, Hasu M, Popov D , et al. Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins[J]. Proc Natl Acad Sci U S A, 1994,91(19):8807-8811.
doi: 10.1073/pnas.91.19.8807
[18] Lalla E, Lamster I, Feit M, et al. Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice[J]. J Clin Invest, 2000,105(8):1117-1124.
doi: 10.1172/JCI8942
[19] Gennaro G, Claudino M, Cestari TM , et al. Green tea modulates cytokine expression in the periodontium and attenuates alveolar bone resorption in type 1 diabetic rats[J]. PLoS One, 2015,10(8):e0134784.
doi: 10.1371/journal.pone.0134784
[1] WU Hongyu,MA Xiaoxin,LU Haixia,FENG Xiping,GU Qin,YE Wei,XIE Yingxin,XIE Danshu,WANG Wenji. Investigation of dental caries and periodontal conditions in maintenance hemodialysis patients [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(5): 313-317.
[2] ZHANG Limu,LIN Xiaoping. Research progress on the mechanism of C-reactive protein mediated periodontitis and systemic diseases [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(3): 184-188.
[3] LI Jiatong,ZHOU Xuedong,XU Xin,WANG Yan. Research progress of probiotics in the prevention and treatment of oral infectious diseases [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(9): 598-601.
[4] DAI Qian,YU Yuanling,HUANG Shiguang. Macrophage IL-33 expression in macrophages of human chronic periapical periodontitis and apical cyst [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(5): 300-303.
[5] XU Xiongcheng,ZHONG Quan,LUO Kai. Application of 3D printing technology in preparation of scaffolds for periodontal tissue regeneration [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(3): 189-193.
[6] ZHU Yanxia,Gegen tana. Research progress of IL-33/ST2 signaling pathway in bone metabolism [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(3): 202-204.
[7] ZHENG Jiawei,ZHAO Zeliang. Progress in the genetics research of infantile hemangioma and vascular malformations [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 749-756.
[8] WANG Ye,LIN Xiaoping. Research progress on the common risk factors and related mechanisms of periodontitis and osteoporosis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 794-798.
[9] WANG Min, GE Song. Research progress on the T cell receptor CDR3 spectral sequence of periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 799-803.
[10] MA Yao,JIANG Zhaowei,JIN Yunyi,MIAO Qian,ZHANG Chunxiang,ZHANG Linkun. Gene ontology analysis of the TNF signaling pathway in early orthodontic tooth movement of rats with periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(11): 695-702.
[11] GUO Xinwei,ZHAO Hongyan,YANG Yaoyao,QIAN Xin,LING Xiaoxu,ZHANG Zhimin. Research progress of periodontitis and periodontal dysbiosis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(11): 739-744.
[12] YIN Xiaoping,XIONG Huacui,CHEN Ke,HUANG Ying,XU Shuaimei. The effects of leptin on osteogenesis/odontogenic related gene expression of human apical papillary stem cells [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(1): 23-29.
[13] CHEN Faming,GAO Lina,CHEN Fang. Current status and progress of periodontal regeneration therapy [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(1): 9-16.
[14] Yi DING,Qi WANG. Therapeutic progress of diabetic periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(9): 545-550.
[15] Zhenzhe LIU,Liang ZHAO,Huairong HUANG,Wenxia HUANG,Hongbai CHEN. Study of the Er: YAG laser in periodontal flap surgery for the treatment of chronic periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(9): 574-577.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2016, 24(2): 125 -128 .
[2] Hong-chang LAI,Jun-yu SHI. Maxillary sinus floor elevation[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2017, 25(1): 8 -12 .
[3] Pin ZHOU, Yang-fei LI. MRI study of temporomandibular joint disc position in asymptomatic volunteers[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2017, 25(4): 239 -244 .
[4] Xinxin XIA, Fang FANG, Lijuan CHENG. Shaping ability of Pathfile and WaveOne in simulated root canals[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2017, 25(6): 365 -368 .
[5] Yuanhong LI, Xinyi FANG, Yu QIU, Lei CHENG. Experimental study on the effects of green tea on salivary flow rate and pH value[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2017, 25(9): 560 -564 .
[6] Chengzhang LI. Masticatory muscles in occlusion[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2017, 25(12): 755 -760 .
[7] . [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(1): 1 .
[8] Zhirong WU, Shiguang Huang. Research progress on the etiology, clinical examination and treatment of peri-implantitis[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(6): 401 -405 .
[9] Xiaowu YAO, Shisheng CHEN, Zizheng LU, Minxiao LIN. Clinical report and literature review on the amyloidosis of salivary glands[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(8): 533 -536 .
[10] Lan LIAO, Lijun ZENG. Updated research on digitalization in aesthetic restoration[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2018, 26(7): 409 -414 .

Copyright © Editorial Board of Journal of Prevention and Treatment for Stomatological Diseases

This work is licensed under a Creative Commons Attribution 3.0 License.

Address:Guangzhou City Jiangnan Road South 366, Editorial office ofJournal of Prevention and Treatment for Stomatological Diseases, zip code: 510280　Fax:020-34304115　E-mail：kqjbfz@vip.126.com

Supported by:Beijing Magtech

This work is licensed under a Creative Commons Attribution 3.0 License.