The Effect of Diabetes Mellitus on the Thickness of Gingival Junctional Epithelium (Study in the Experiment of Caspase-3)

Abdelaziz Eljawadi(1*), Totok Utoro(2), Nunuk Purwanti(3)

(1) Department of Prosthodontic, Faculty of Dentistry, Almergeb University
(2) Departement of Pathology Anatomy, Faculty of Medicine, Gadjah Mada Univesity
(*) Corresponding Author


Diabetes mellitus (DM) is a metabolic disorder manifested by abnormally high levels of blood glucose, resulting in hyperglycemia that affects the oral cavity, leading to periodontitis. The junctional epithelium (JE) is the epithelial component of the dento-gingival unit that is in contact with the toothsurface. Apoptosis and proliferation of JE are essential to maintenance JE thickness.  Apoptosis is programmed cell death that can be triggered by various signals and is characterized by well-defined morphologic changes and biochemical features. Caspase-3 is involved in the underlying mechanisms of apoptosis, and the activation of caspase-3 is considered to be the final step in many apoptosis pathways. Purpose of this study was to investigate the effect of DM on the expression of caspase-3 and the thickness of JE. Sixteen male Sprague-Dawley rats were used and divided equally into two groups: the diabetic group that injected intraperitoneal by streptozotocin (STZ) and negative control group. Measurements of blood glucose levels were analyzed before and at 2, 4 weeks after STZ injection. In addition, JE thickness and expression of caspase-3 were examined after 2 and 4 weeks. JE was stained by hematoxylin-eosin (H&E) staining for thickness measurement and the immunohistochemistry by using the anti-caspase-3 antibody for caspase-3 expression measurement and examined under light microscope. The results of the present study showed that a decrease of JE thickness and increase of caspase-3 expression were obtained while increasing the diabetic duration. Two ways Anova and Least Significant Difference (LSD) tests indicated a significant difference of JE thickness and caspase-3 expression between all groups except in diabetic group after 2 and 4 weeks. Also, caspase-3 expression in diabetic group after 2 and 4 weeks (P > 0.05) were not significantly different. It can be concluded that diabetes mellitus (DM) affected on the thickness and caspase-3 expression of JE. Furthermore, the results suggest that high expression of caspase-3 was associated with the diabetes-induced apoptotic cell-death resulting in reduction of JE thickness.


Streptozotocin; diabetes mellitus; junctional epithelium; expression of caspase-3

Full Text:



Yoo-Jung, U.M., Jung, U.W., Kim, C.S., Bak, E.J., Cha, J.H., Yoo, Y.J., Choi, S.H., 2010, The Influence of Diabetes Mellitus on Periodontal Tissues: A Pilot

Study, J Perio Imp Sci; 40:49-55 • doi:10.5051/jpis.40.2.49.J. Clerk Maxwell,

A Treatise on Electricity and Magnetism, 3rd ed., Vol. 2. Oxford:

Clarendon, 1892, pp. 68–73.

Abeeleh, M.A., Ismail, Z.B., Alzaben, K.R., Halaweh, S.A., Essa, M.K., Abuabeeleh, J., Alsmady, M.M., 2009, Induction of Diabetes Mellitus in Rats Using

Intraperitoneal Streptozotocin: A Comparison between 2 Strains of Rats,

E. J.P., Inc; ISSN 1450-216X Vol.32 No.3, pp.398-402.K. Elissa, “Title of

paper if known,” unpublished.

Akbarzadeh, A., Norouzian, D., Mehrabi, M.R., Farhangi, A., Verdi, A.A.,

Mofidian, S.M.A., Rad, B.L., 2007, Induction of Diabetes by

Streptozotocin In Rats, J Biol Chem; 22 (2) 60-64.Y. Yorozu, M. Hirano, K.

Oka, and Y. Tagawa, “Electron spectroscopy studies on magnetooptical media and plastic substrate interface,” IEEE Transl. J. Magn. Japan, Vol. 2, pp. 740–741, August 1987 [Digests 9th Annual Conf. Magnetics Japan, p. 301, 1982].

Bosshardt, D.D., Lang, N.P., 2005, The Junctional Epithelium: from Health to

Disease, Dent Res; 84(1):9-20.

Cai, L., Wei, L., Wang, G., Guo, L., Jiang,Y., Kang, Y.J., 2002, HyperglycemiaInduced Apoptosis in Mouse:Myocardium Mitochondrial

Cytochrome c–Mediated Caspase-3 Activation Pathway, Diabetes; 51:


Claudino, M., Ceolin, D.S., Alberti, S.,Cestari, T.M., Spadella, C.T., Rubira,

L.R.F., Garlet, G.P., Assis, G.F.D., 2007, Alloxan-Induced Diabetes Triggers the Development of Periodontal Disease in Rats, PLoS ONE;2(12): e1320. Doi:

1371/ journal.pone.0001320.

Fullgrabe, J., Hajji, N., Joseph, B., 2010, Cracking the Death Code:

Apoptosis Related Histone Modifications, Cell Death and Differentiation; Am J Respir Crit Care Med; 17, 1238–1243.

Graves, D.T., Liu, R., Alikhani, M., Mashat, H., Trackman, P.C., 2006,

Diabetes-enhanced Inflammation and Apoptosis—Impact on Periodontal

Pathology, J Dent Res; 85(1):15-21.

Hagerkvist, R., Makeeva, N., Elliman, S., Welsh, N., 2006, Imatinib Mesylate (Gleevec) Protects Against Streptozotocin-Induced Diabetes and

Islet Cell Death in Vitro, Cell Biol Inter; 30,1013e1017.

Kantarci, A., Augustin, P., Firatli, E., Sheff, M.C., Hasturk, H., Graves, D.T.,

Trackman P.C., 2007, Apoptosis in Gingival Overgrowth Tissues, J Dent Res;


Khan, S.Y., 2009, Short communication: Diabetes and its implication in

periodontics, Biomedical Research; 20(2): 87-88.

Lalla, E., Cheng, B., Lal, S., Kaplan, S., Softness, B., Greenberg, E., Goland, R.S., Lamster, I.B., 2007, Diabetes Mellitus Promotes Periodontal Destruction in Children, J Clin Periodontol; 34: 294–298. doi: 10.1111/j; 1600-051X.2007.01054.x.

Lenzen, S., 2008, The Mechanisms of Alloxan- and Streptozotocin-Induced Diabetes, Diabetologia, J Dent Res; 51:216–226.

Lu, Y.Y., Chen, T.S., Jun-Le, Q., Pan, W.L., Sun, L., Wei, X.B., 2009,

Dihydroartemisinin (DHA) Induces Caspase-3-Dependent Apoptosis in

Human Lung Adenocarcinoma ASTC-A-1 Cells, J Bioml S; 16:16


Matthews, D.C., 2002, The Two-Way Relationship Between Diabetes and

Periodontal Disease, Can Dent A; 68(3):161-164.

Mealey, B.L., Oates, T.W., 2006, Diabetes Mellitus and Periodontal

Diseases, J Perio Res; 77:1289-1303.

Oksanenl, J., Sorokin, L.M., Virtanen, H.M., 2001, The Junctional Epitlelium around Murine Teeth differs from Gingival Epithelium in its Basement Membrane Composition, J Dent Res; 80(12):2093-2097.

Paul, A.J.K., Suat, S.H.W., Niessen, M., 2009, Apoptosis in Diabetes, Apoptosis, J Dent Res; 10.1007/s10495-0090419-6.

Porter, A.G., Janicke, R.U., 1999, Emerging Roles of Caspase-3 in

Apoptosis, Cell Death andDifferentiation, J Dent Res; 6, 99 - 104.

Silvestre, F.J., Miralles, L., Llambes, F., Bautista, D., Izquierdo, E.S., Mijares, A.H., 2009, Type 1 Diabetes Mellitus and Periodontal Disease:

Relationship to Different Clinical Variables, Med Oral Patol Oral Cir

Bucal; 1;14 (4):E175-9.

Szkudelski, T., 2001, The Mechanism of Alloxan and Streptozotocin Action in β-Cells of the Rat Pancreas, Physiol Res; 2001.50: 536-546

Tan, W.C., Tay, F.B.K., Lim, L.P., 2006, Diabetes as a Risk Factor for

Periodontal Disease: Current Status and Future Considerations, Ann Acad

Med Sin; 35:571-81.

Tao, Y., KIM, J., Stanley, M., Zhibin, H., Faubel, S., Robert, W.S., Edelstein C.L., 2005, Pathways Of Caspase-Mediated Apoptosis in Autosomal-Dominant

Polycystic Kidney Disease (ADPKD), Kidney, J Perio Imp Sci; Vol. 67; pp. 909–919.

Sasaki, Au., Yamada, T., Inoue, K., Momoil, T., Tokunaga, H., Sakiyama, K.,

Kanegae, H., Suda, N., and Amano, O., 2011, Localization of Heat Shock Protein 27 (Hsp27) in the Rat Gingiva and its Changes with Tooth Eruption,

Acta Histochem Cyto chem; 44 (1): 1724;doi:10.1267/ahc.10033.

Tesseromatis, C., A. Kotsiou, H., Parara, E., Vairaktaris, M., Tsamouri.,

, Morphological Changes of Gingiva in Streptozotocin Diabetic Rats,

I J Dent;ID725628,doi:10.1155;725628.


Article Metrics

Abstract views : 164 | views : 128


  • There are currently no refbacks.





website statistics


View My Stats