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Journal of Dental Research
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Glucose-mediated Alteration of Cellular Function in Human Periodontal Ligament Cells

F. Nishimura

Department of Periodontology and Endodontology, Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700, Japan

V. Terranova

Laboratory of Tumor Biology and Connective Tissue Research, Columbia University School of Dental and Oral Surgery, 630 W. 168th Street, New York, New York 10032, (current adress) Edward Hines Jr. Hospital, 151 Research Service, Hine, Illinois 60141

H. Foo

Laboratory of Tumor Biology and Connective Tissue Research, Columbia University School of Dental and Oral Surgery, 630 W. 168th Street, New York, New York 10032

M. Kurihara

Department of Periodontology and Endodontology, Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700, Japan

H. Kurihara

Department of Periodontology and Endodontology, Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700, Japan

Y. Murayama

Department of Periodontology and Endodontology, Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700, Japan, to whom correspondence and reprint requests should be addressed

Because diabetic patients are easily led to manifest severe periodontitis, we wanted to determine whether various glucose levels interfere with normal cellular function. Human periodontal ligament (PDL) cells were cultured in glucose-free medium, or in medium containing either 1100 mg/L of glucose (normal-glucose medium) or 4500 mg/L of glucose (high-glucose medium). Cells cultured in glucose-free medium changed their morphology from spindle-shaped to round, and incorporated trypan blue in a time-dependent manner. The incorporation rate was much faster in cells with shorter cell cycles than in those with longer cycles, suggesting the involvement of cell-cycle progression in cell death. However, fragmented DNA, which suggests apoptotic cell death, was not observed in these cells. We reasoned that initial cell rounding and detachment from the culture plate might be due to the conformational changes in cell-surface receptors to fibronectin, a major extracellular matrix for fibroblasts. Western blot analysis revealed that cells cultured in glucose-free medium lost their fibronectin receptor in a time-dependent manner. In addition, fibronectin receptor expression was much higher in cells cultured in high-glucose medium than in cells cultured in normal-glucose medium. Furthermore, the over-expression of the fibronectin receptor resulted in a suppressed chemotactic response of these cells to platelet-derived growth factor. On the basis of these data, it was hypothesized that a high glucose level induced over-expression of these receptors. This might be the mechanism by which a high glucose level compromises wound healing in diabetic patients and, at least in part, might be the reason diabetic patients are subject to severe periodontal destruction.

Key Words: glucose • periodontal ligament cells • cell death • fibronectin receptor • chemotaxis.

REFERENCES

  • Ayo SH, Radnic RA, Glass WF 2nd, Garoni JA, Rampt ER, Appling DR, et al. (1991). Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium. Am J Physiol 260:F185-F191.[Medline] [Order article via Infotrieve]
  • Bacic M., Plancak D., Granic M. (1988). CPITN assessment of periodontal disease in diabetic patients. J Periodontol 59:816-822.[Medline] [Order article via Infotrieve]
  • Benveniste R., Bixler D., Conneally PM (1967). Periodontal disease in diabetics. J Periodontol 38:271-279.[Medline] [Order article via Infotrieve]
  • Boehme SA, Lenardo MJ (1993). Propriocidal apoptosis of mature T lymphocytes occurs at S phase of the cell cycle. Eur J Immunol 23:1552-1560.[Medline] [Order article via Infotrieve]
  • Boyan LA, Bhargava G., Nishimura F., Orman R., Price R., Terranova VP (1994). Mitogenic and chemotactic responses of human periodontal ligament cells to the different isoforms of platelet-derived growth factor. J Dent Res 73:1593-1600.
  • Cagliero E., Roth T., Roy S., Lorenzi M. (1991). Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endothelial cells. Diabetes 40:102-110.[Abstract]
  • Cohen DW, Friedman LA, Shapiro J., Kyle GC, Franklin S. (1970). Diabetes mellitus and periodontal disease: Two-year longitudinal observations. Part I. J Periodontol 41:709-712.
  • Cohen GM, Sun X.-M, Snowden RT, Dinsdale D., Skilleter DN (1992). Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J 286:331-334.[Medline] [Order article via Infotrieve]
  • Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM, Strober W, editors (1992). Current protocols in immunology: Tripan blue exclusion test of cell viability. New York: Green Publishers Association and Wiley-Interscience.
  • Cooper GM (1990). Oncogenes. Boston: Jones and Bartlett Publishers.
  • Dedhar S., Argraves WS, Suzuki S., Ruoslahti E., Pierschbacher MD (1987). Human osteosarcoma cells resistant to detachment by an Arg-Gly-Asp-containing peptide overproduce the fibronectin receptor. J Cell Biol 105:1175-1182.[Abstract/Free Full Text]
  • Emrich LJ, Schlossman M., Genco RJ (1991). Periodontal disease in non-insulin dependent diabetes mellitus. J Periodontol 62:123-131.[Medline] [Order article via Infotrieve]
  • Falcieri E., Martelli AM, Bareggi R., Cataldi A., Cocco L. (1993). The protein kinase inhibitor staurosporine induces morphological changes typical of apoptosis in molt-4 cells without concomitant DNA fragmentation. Biochem Biophys Res Commun 193:19-25.[CrossRef][Medline] [Order article via Infotrieve]
  • Frisch SM, Francis H. (1994). Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619-626.[Abstract/Free Full Text]
  • Giancotti FG, Ruoslahti E. (1990). Elevated levels of the {alpha}5β1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell 60:849-859.[CrossRef][Medline] [Order article via Infotrieve]
  • Gregoire V., Van NT, Stephens LC, Brock WA, Milas L., Plunkett W., et al. (1994). The role of fludarabine-induced apoptosis and cell cycle synchronization in enhanced murine tumor radiation response in vivo. Cancer Res 54:6201-6209.[Abstract/Free Full Text]
  • Harlow E., Lane D. ( 1988). Antibodies: A laboratory mannual. New York: Cold Spring Harbor Laboratory Press.
  • Hove KA, Stallard RE (1970). Diabetes and the periodontal patient. J Periodontol 41:713-718.[Medline] [Order article via Infotrieve]
  • Hugoson A., Thorstensson H., Falk H., Kuylenstierna J. (1989). Periodontal conditions in insulin dependent diabetics. J Clin Periodontol 16:215-223.[CrossRef][Medline] [Order article via Infotrieve]
  • Katz PP, Wirthlin MR Jr, Szpunar SM, Selby JV, Sepe SJ, Showstack JA (1991). Epidemiology and prevention of periodontal disease in individuals with diabetes. Diabetes Care 14:375-385.[Abstract]
  • Laemmli UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685.[CrossRef][Medline] [Order article via Infotrieve]
  • Li
  • W, Shen S., Khatami M., Rockey JH (1984). Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high-glucose concentration. Diabetes 33:785-789.[Abstract]
  • Loe H. (1993). Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care 16:329-334.[Medline] [Order article via Infotrieve]
  • Lorenzi M., Cagliero E. (1991). Pathobiology of endothelial and other vascular cells in diabetes mellitus.Diabetes 40:653-659.[Abstract]
  • Massague J. (1990). The transforming growth factor-beta family. Ann Rev Cell Biol 6:597-641.[CrossRef]
  • Matsuda N., Lin W.-L, Kumar NM, Cho MI, Genco RJ (1992). Mitogenic, chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. J Periodontol 63:515-525.[Medline] [Order article via Infotrieve]
  • Meredith JE Jr, Fazeli B., Schwartz MA (1993). The extracellular matrix as a cell survival factor. Mol Biol Cell 4:953-961.[Abstract]
  • Oates TW, Rouse CA, Cochran DL (1993). Mitogenic effects of growth factors on human periodontal ligament cells in vitro. J Periodontol 64:142-148.[Medline] [Order article via Infotrieve]
  • Oberhammer F., Fritsch G., Schmied M., Pavelka M., Printz D., Purchio T., et al. (1993). Condensation of the chromatin at the membrane of an apoptotic nucleus is not associated with activation of an endonuclease. J Cell Sci 104:317-326.[Abstract]
  • Oliver RC, Tervonen T. (1994). Diabetes-A risk factor for periodontitis in adults? J Periodontol 65:530-538.[Medline] [Order article via Infotrieve]
  • Ragnarsson B., Carr G., Daniel JC (1985). Isolation and growth of human periodontal ligament cells in vitro. J Dent Res 64:1026-1031.
  • Roth T., Podesta F., Stepp MA, Boeri D., Lorenzi M. (1993). Integrin overexpression induced by high glucose and by human diabetes: Potential pathway to cell dysfunction in diabetic microangiopathy. Proc Natl Acad Sci USA 90:9640-9644.[Abstract/Free Full Text]
  • Roy S., Sala R., Cagliero E., Lorenzi M. (1990). Overexpression of fibronectin induced by diabetes or high glucose: Phenomenon with a memory. Proc Natl Acad Sci USA 87:404-408.[Abstract/Free Full Text]
  • Schiffman E., Gallin JI (1979). Biochemistry of phagocyte chemotaxis. In: Current topics in cell regulation. Vol. 15. Horecker BL, Stadtman ER, editors. New York: Academic Press, pp. 203-216.
  • Schulze-Osthoff K., Walczak H., Droge W., Krammer PH (1994). Cell nucleus and DNA fragmentation are not required for apoptosis. J Cell Biol 127:15-20.[Abstract/Free Full Text]
  • Schwartz LM, Smith SW, Jones ME, Osborne BA (1993). Do all programmed cell deaths occur via apoptosis? Proc Natl Acad Sci USA 90:980-984.[Abstract/Free Full Text]
  • Shan B., Lee WH (1994). Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol Cell Biol 14:8166-8173.[Abstract/Free Full Text]
  • Sznajder N., Carraro JJ, Rugna S., Sereday M. (1978). Periodontal findings in diabetic and non-diabetic patients. J Periodontol 49:445-448.[Medline] [Order article via Infotrieve]
  • Terranova VP, Odziemiec C., Tweden KS, Spadone DP (1989). Repopulation of dentin surfaces by periodontal ligament cells and endothelial cells. Effect of basic fibroblast growth factor. J Periodontol 60:293-301.[Medline] [Order article via Infotrieve]
  • Tervonen T., Knuuttila M. (1986). Relation of diabetes control to periodontal pocketing and alveolar bone level. Oral Surg Oral Med Oral Pathol 61:346-349.[Medline] [Order article via Infotrieve]

Journal of Dental Research, Vol. 75, No. 9, 1664-1671 (1996)
DOI: 10.1177/00220345960750090801


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