Effect of Glucose at High Concentrations on the Apoptosis of the Cultured Periodontal Ligament Cells and Osteoblasts

고농도 포도당이 뼈모세포와 치주인대세포의 세포자멸사에 미치는 영향에 관한 연구

  • Park, Sung-Ho (Department of Oral Anatomy, School of Dentistry, Kyung Hee University) ;
  • Jue, Seong-Suk (Department of Oral Anatomy, School of Dentistry, Kyung Hee University) ;
  • Hong, Jung-Pyo (Department of Oral Medicine, School of Dentistry, Kyung Hee University) ;
  • Shin, Je-Won (Department of Oral Anatomy, School of Dentistry, Kyung Hee University)
  • 박성호 (경희대학교 치의학전문대학원 구강해부학교실) ;
  • 주성숙 (경희대학교 치의학전문대학원 구강해부학교실) ;
  • 홍정표 (경희대학교 치의학전문대학원 구강내과학교실) ;
  • 신제원 (경희대학교 치의학전문대학원 구강해부학교실)
  • Published : 2007.12.30


This experiment was designed to clarify the effect of extracellular glucose on the osteoblasts and periodontal ligament cells. The cells were incubated for 24 and 48 hours with ${\alpha}$-MEM including 1,000 mg/L (control group) and 4,500 mg/L (experimental group) of glucose. Then, the expressions of caspase-3, p38 MAPK, JNK-1, and ERK-1 were examined using Elisa assay and Western blot. The results were as follows: 1. The expression of caspase-3 and p38 MAPK was increased by the high extracellular glucose in both cells. 2. The expression of caspase-3 and p38 MAPK was increased greatly in the periodontal ligament cells than the E1 cells by the high extracellular glucose. 3. The expression of JNK-1 was increased by the high extracellular glucose in both cells. 4. The expression of ERK-1 was not changed by the high extracellular glucose in both cells. These results suggest that extracellular glucose at high concentrations may inhibit the periodontal regeneration process increasing cellular apoptosis. And p38 MAPK and JNK-1 pathway may be the most responsible intracellular pathway rather than ERK-1.


  1. Auwerx J, Dequeker J, Bouillon R, Geusens P, Niijs J. Mineral metabolism and bone mass at peripheral and axial skeleton in diabetes mellitus. Diabetes 1988 37:8-12 https://doi.org/10.2337/diabetes.37.1.8
  2. Hui SL, Epstein S, Johnson CC Jr. A prospective study of bone mass in patients with type I diabetes. J Clin Endocrinol Metab 1986;60:74-80 https://doi.org/10.1210/jcem-60-1-74
  3. Ho FM, Liu SH, Liau CS, Huang PJ, Lin-Shiau SY. High glucose induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH2-terminal kinase and caspase-3. Circulation 2000;101:2618-2624 https://doi.org/10.1161/01.CIR.101.22.2618
  4. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immunol 2002;20:55-72 https://doi.org/10.1146/annurev.immunol.20.091301.131133
  5. Henkart PA. ICE family proteases: mediators of all apoptotic cell death? Immunity 1996;4:195-201 https://doi.org/10.1016/S1074-7613(00)80428-8
  6. Verhaeghe J, Van Herck E, Visser WJ et al. Bone and mineral metabolism in BB rats with long-term diabetes. Diabetes 1990;39:477-482 https://doi.org/10.2337/diabetes.39.4.477
  7. Chang L, Karin M. Mammalian MAP kinase signaling cascades. Nature 2001;410:37-40 https://doi.org/10.1038/35065000
  8. Shin CS. The prevalence of diabetics in yeon-cheon area of Gyeong Gi-do. Korean diabetics 1996;20: 264-270
  9. Schaeffer HJ, Weber MJ. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 1999;19:2435-2444 https://doi.org/10.1128/MCB.19.4.2435
  10. Bouillon R. Diabetic bone disease. Calcif Tissue Int 1991;49:155-160 https://doi.org/10.1007/BF02556109
  11. Shlossman M, Knowler WC, Pettitt DJ, Genco RJ. Type 2 diabetes mellitus and periodontal disease. J Am Dent Assoc 1990;120:532-536
  12. Sasaki T, Kaneko H, Ramamurthy NS, Golub LM. Tetracycline administration restores osteoblast structure and function during experimental diabetes. Anat Rec 1991;231(1):25-34 https://doi.org/10.1002/ar.1092310105
  13. Kudoh S, Komuro I, Minuzo T. Angiotensin II stimulates c-Jun NH2terminal kinase in cultured cardiac myocytes of neonatal rats. Circ Res 1997;80:139-146 https://doi.org/10.1161/01.RES.80.1.139
  14. Min H. The clinical characteristics of Korean diabetic patients. Korean Diabetics 1992;16:163-173
  15. Kumar S. The apoptotic cysteine protease CPP32. Int J Biochem Cell Biol 1997;29:393-396 https://doi.org/10.1016/S1357-2725(96)00146-X
  16. Krakauer JC, McKenna MJ, Buderer NF, Rao DS, White-house FW, Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes 1995;44:775-782 https://doi.org/10.2337/diabetes.44.7.775
  17. Xia Z, Dickens M, Raingeaud J. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science1995;270:1326-1331 https://doi.org/10.1126/science.270.5240.1326
  18. Khan CR. Insulin resistance. A common feature of diabetes mellitus. N Eng J Med 1986;315:252 https://doi.org/10.1056/NEJM198607243150410
  19. Emrich LJ, Schlossman M, Genco RJ. Periodontal disease in non-insulin-dependent diabetes mellitus. J Periodontol 1991 62:123-130 https://doi.org/10.1902/jop.1991.62.2.123
  20. Ervasti T, Knutilla M, Pohjamo L, Haukipuro K. Relation between control of diabetes and gingival bleeding. J Periodontol 1985;56:154-157 https://doi.org/10.1902/jop.1985.56.3.154
  21. Komuro I, Kudo S, Yamazaki T. Mechanical stretch activates the stress-activated protein kinases in cardiac myocytes. FASEB J 1996;10:631-636 https://doi.org/10.1096/fasebj.10.5.8621062
  22. Villa P, Kaufmann SH, Earnshaw WC. Caspases and caspase inhibitors. Trends Biochem Sci 1997;22(10): 388-393 https://doi.org/10.1016/S0968-0004(97)01107-9
  23. Thorstensson H, Hugosen A. Periodontal disease experience in adult long duration insulin-dependent diabetics. J Clin Periodontol 1993;20:352-358 https://doi.org/10.1111/j.1600-051X.1993.tb00372.x
  24. Botolin S, Faugere MC, Malluche H, Orth M, Meyer R, McCabe LR. Increased bone adiposity and peroxisomal proliferator-activated receptor-gamma2 expression in type I diabetic mice. Endocrinology 2005;146:3622-3631 https://doi.org/10.1210/en.2004-1677
  25. Platanias LC. Map kinase signaling pathways and hematologic malignancies. Blood 2003;101:4667-4679 https://doi.org/10.1182/blood-2002-12-3647
  26. Wang X, Zelenski NG, Yang J. Cleavage of sterol regulatory element binding protein (SREBPs) by CPP32 during apoptosis. EMBO J 1996;15:1012-1020
  27. Raman M, Chen W, Cobb MH. Differential regulation and properites of MAPKs. Oncogene 2007;26: 3100-3112 https://doi.org/10.1038/sj.onc.1210392