The Effect of TGF-{\beta}_1 on Cellular Activity of Periodontal Ligament Cells activated by PDGF-BB

PDGF-BB에 의한 치주인대세포활성에 대한 TGF-{\beta}의 효과

  • Baek, Sang-Churl (Department of Periodontology, College of Dentistry Kyungpook National University) ;
  • Park, Jin-Woo (Department of Periodontology, College of Dentistry Kyungpook National University) ;
  • Suh, Jo-Young (Department of Periodontology, College of Dentistry Kyungpook National University)
  • 백상철 (경북대학교 치과대학 치주과학교실) ;
  • 박진우 (경북대학교 치과대학 치주과학교실) ;
  • 서조영 (경북대학교 치과대학 치주과학교실)
  • Published : 2002.09.30

Abstract

The purposes of this study is to evaluate the combination effects of TGF-${\beta}_1$ and PDGF-BB on the periodontal ligament cells to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM/100% FBS at the $37^{\circ}C$, 5% $CO_2$ incubator. Authors measured the DNA synthesis, total protein, collagen and noncollagenous protein synthesis according to the concentration of TGF-${\beta}_1$,(1,5ng/ml) and PDGF-BB (1,10 ng/ml) in combination. To explore further this delayed effect of TGF-${\beta}_1$, we preincubated human periodontal ligament cells with TGF-${\beta}_1$ for 4 or 24 hours before PDGF-BB stimulation. The results were as follows: The DNA synthetic activity was increased dose dependently by TGF-${\beta}_1$, PDGF-BB. The combination of TGF-${\beta}_1$ and PDGF-BB consistently enhanced the DNA synthetic activity to PDGF-BB alone. The ability of TGF-${\beta}_1$ to enhance DNA synthetic activity in PDGF-BB treated periodontal ligament cells was dose dependent. The maximum mitogenic effect was at the 5ng/ml of TGF-${\beta}_1$ and l0ng/ml of PDGF-BB. Preincubation of cell with TGF-${\beta}_1$ resulted in significantly greater response to PDGF-BB at all TGF-${\beta}_1$ concentration studied, and may be useful for clinical application in periodontal regenerative procedures. The total protein, collagen and noncollagen synthesis was increased dose pendently by TGF-${\beta}_1$, PDGF-BB. The % of collagen was slightly decreased according to the concentration of TGF-${\beta}_1$, PDGF-BB. The effect of TGF-${\beta}_1$, PDGF-BB were not specific for collagen synthesis since it also increased noncollagenous protein synthesis. This study demonstrates that PDGF-BB is major mitogens for human periodontal ligament cells in vitro, and supports a role for TGF-${\beta}_1$ as a regulation of the mitogenic and total protein formation to PDGF-BB in these cells.

이 연구는 배양된 치주인대세포에 TGF(Transforming growth factor)-${\beta}_1$과 PDGF(Plateletderived growth factor)-BB를 농도별로 혼합 주입해서 세포의 증식능, 단백질 및 교원질 합성능을 측정해 봄으로서 TGF-${\beta}_1$ 이 치주인대세포의 중식과 활성에 대한 PDGF-BB의 효과를 상승시킬 수 있은지 알아보고자 본 실험을 실시하였다. 교정치료를 위해 내원한 환자로 부터 건강한 제일소구치를 발거하여 치주인대세포률 분리, 배양하여 TGF-${\beta}_1$과 PDGF-BB를 동시에 주입한 군과 TGF-${\beta}_1$를 4, 24시간 전처리 배양한 군과 나누어 실험하였다. TGF-${\beta}_1$, PDGF-BB를 주입하지 않은군을 대조군으로 하여 DNA 합성능, 총단백질과 교원질 합성능을 측정하여 다음과 같은 결과를 얻었다. 치주인대세포에 TGF-${\beta}_1$과 PDGF-BB을 동시 주입하였을 때 DNA 합성능의 효과는 대조군에 비해 모든 군에서 증가된 양상을 보였으며 1ng/ml PDGF-BB 투여군에 비해 10ng/ml PDGF-BB 투여군에서 증가 양상이 높았고 PDGF-BB 단독 투여군보다 TGF-${\beta}_1$병용 투여군에서 DNA 합성능이 증가된 양상을 나타내었으며 5ng/ml TGF-${\beta}_1$과 10ng/ml PDGF-BB 투여군에서 가장 높은 증가 양상을 보였다. TGF-${\beta}_1$ 4시간과 24시간 전처리 배양군 양군 공히 lng/ml PDGF-BB 투여군을 제외한 모든 군에서 대조군에 비해 증가된 양상을 보였으며 lng/ml PDGF-BB 투여군에 비해 10ng/ml PDGF-BB 투여군에서 증가 양상이 더 높았고 PDGF-BB 단독 투여군보다 TGF-${\beta}_1$ 전 처리군에서 DNA 합성능이 증가된 양상을 나타내 였으며 5ng/ml TGF-${\beta}_1$ 전 처리 후 10ng/ml PDGF-BB 투여군에서 가장 높은 증가 양상을 보였다. 치주인대세포에 TGF-${\beta}_1$과 PDGF-BB을 동시 주입하였을 때 총단백질합성량은 대조군에 비해 모든 군에서 증가된 양상을 보였으며 lng/ml PDGF-BB 투여군에 비해 10ng/ml PDGF-BB 투여군에서 증가 양상이 더 높게 나타났다. PDGF-BB 단독 투여군보다 TGF-${\beta}_1$ 병용 투여군에서 총단백칠 합성양이 증가된 양상을 나타내었다. TGF-${\beta}_1$ 4과 24시간 전처리 배양군의 총단백질 합성양은 대조군에 비해 모든 군에서 증가된 양상을 보였으며 1ng/ml PDGF-BB 투여군에 비해 10ng/ml PDGF-BB 투여군에서 증가 양상이 더 높았고 TGF-${\beta}_1$ 전처리 배양군이 PDGF-BB 단독 투여군보다 총단백질 합성양이 증가된 양상을 나타내었다. TGF-111과 PDGF-BB를 동시 투여하였을 때 대조군에 비해 모든 군에서 교원질 합성능이 증가하는 경향을 나타내었으며, 비교원성단백질의 합성능은 1, 10ng/ml PDGF-BB 단독투여군을 제외하고 대조군에 비해 증가하는 경향을 보였다. 총단백질에 대한 교원질 합성의 상대적 비율 PDGF-BB 단독 투여군보다 TGF-${\beta}_1$ 병용 투여군에서 감소하는 정향을 나타내었다. TGF-${\beta}_1$ 4과 24시간 전처리 배양군의 교원질과 비교원성 단백질 합성능은 대조군에 비해 모든 군에서 교원질과 비교원성 단백질 합성능이 증가하는 경향을 나타내었으며 PDGF-BB 단독 투여군보다 TGF-${\beta}_1$ 병용 투여군에서 총단백질 합성양이 증가된 양상을 나타내었으며 그 정도는 TGF-${\beta}_1$의 농도 의존적인 양상을 보였다. 총단백질에 대한 교원질 합성의 상대적비율은 TGF-${\beta}_1$ 4,24시간전처리 배양군 모두에서 대조군에 비해 감소하는 경향을 나타내었다. 이상의 결과를 종합해 볼 때 치주인대세포에서 TGF-${\beta}_1$은 PDGF-BB의 기능을 조절하는 능력을 가지고 있으며 두 성장인자 주입시 동시주입시보다 TGF-${\beta}_1$을 전처리 해 줌으로써 PDGF-BB의 반응을 더욱 촉진시킬 수 있음을 알 수 있었다.

Keywords

References

  1. Nyman, S., Karring, T., Lindhe.J, and Platen, S. : Healing following implantation of periodontitisaffected roots into gingival connective tissue, J. Clin. Periodontol., 7: 394-401, 1980 https://doi.org/10.1111/j.1600-051X.1980.tb02012.x
  2. Gould,T. R. L.,Melcher, A. H. and Brunette, D. M. : Migration and division of progenitor cell populations in periodontal ligament after wounding.J, Periodont. Res., 15 : 20-42, 1980 https://doi.org/10.1111/j.1600-0765.1980.tb00258.x
  3. McCulloch, C. A. G. : Progenitor cell populations in the periodontal ligament of mice, Anat. Rec., 211 : 258-262, 1985 https://doi.org/10.1002/ar.1092110305
  4. Davidson, L. and McCulloch, C. A. G. : Proliferative behavior of periodontal ligament cell populations, J. Periodont. Res., 21: 414-428, 1986 https://doi.org/10.1111/j.1600-0765.1986.tb01475.x
  5. Aukhil, I., Simpson, D. M., Suggs, C. and Pettersson, E. : In vivo differentiation of progenitor cells of the periodontalligament : An experimental study using physical barriers, J. Clin, Periodontol., 13 : 862-868, 1986 https://doi.org/10.1111/j.1600-051X.1986.tb02244.x
  6. Shore, R. C. and Berkovitz, B. K. B. : An ultra structural study of periodontal ligament fibroblasts in relation to their possible role in tooth eruption and intracellular collagen degradation in the rat, Archs. Oral Biol., 24 : 155-164, 1979 https://doi.org/10.1016/0003-9969(79)90064-5
  7. Nyman, S., Gottlow, J., Karring, T. and Lindhe, J. : The regenerative potential of the periodontal ligament: An experimental study in the monkey, J. Clin. eriodontol., 9 : 257-265, 1982 https://doi.org/10.1111/j.1600-051X.1982.tb02065.x
  8. Narayanan, A. S. and Page, R. C. : Connective tissue of the periodontium : A summary of current work, Collagen ReI. Res., 3 : 33-64, 1983 https://doi.org/10.1016/S0174-173X(83)80048-X
  9. Femyhough, W. and Page, R. C. : Attachments, growth and synthesis by human gingival fibroblasts on demineralized or fibronectin-treated normal and diseased tooth roots, J. Periodontol., 54 : 133-140, 1983 https://doi.org/10.1902/jop.1983.54.3.133
  10. Kleinman, H. K., Klebe, R. J. and Martin, G. R. : Role of collagenous matrices in the adhesion and growth of cells. J. Cell BioI., 92 : 473-479, 1981
  11. Terranova, V. P., Nishimura, F., Price, R. M., Ye, J. : Polypeptide stimulation of periodontal regeneration, Periodont. Case Rep., 13 : 6-12, 1991
  12. Terranova, V. P., and Wikesj?, U. M. E. : Extracellular matrices and polypeptide growth factors as mediators of functions of cells of the periodontium, J. eriodontol., 58: 371-380, 1987 https://doi.org/10.1902/jop.1987.58.6.371
  13. Graves, D. T. and Cochran, D. L. : Mesenchymal cell growth factors, Crit, Rev. Oral BioI. Med., 1 : 17-36, 1990 https://doi.org/10.4197/Med.1-1.3
  14. Hintz, R. L. and Liu, J. : Demonstration of specific plasma protein binding sites for somatomedin, J. Clin, Endocrinol. Metab., 45 : 988-995, 1977 https://doi.org/10.1210/jcem-45-5-988
  15. Ross, R., Raines, E. W. and Bowen-Popo, f. : The biology of platelet-derived growth factor, Cell, 46 : 155-169, 1986 https://doi.org/10.1016/0092-8674(86)90733-6
  16. Stiles, C. D. : The molecular biology of platelet-erived growth factor, Cell, 33: 653-659, 1983 https://doi.org/10.1016/0092-8674(83)90008-9
  17. Kohler, N. and Lipton, A. : Platelet as a source of fibroblast growth promoting activity, Exp, Cell Res, 87 : 297-301 : 1974 https://doi.org/10.1016/0014-4827(74)90484-4
  18. Antoniades, H. N. : Human platelet-derived growth factor(PDGF) : Purification of PDGF- I and PDGF-II and separation of their reduced subunits, Proc, Natl, Acad, Sci. U.S.A., 78 : 7314-7317, 1981 https://doi.org/10.1073/pnas.78.12.7314
  19. Deuel, T. F., Huang, J. S., Proffit, R. I., Baenzinger, J. U., Chang, D. and Kennedy, B. B. : Human platelet-derived growth factor purification and resolution into two active protein fractions. J, BioI. Chem., 256: 8896-8899, 1981
  20. Heldin, C. H. , Backstrom, G. and Ostman, A. : Binding of different dimetric forms of PDGF to human fibroblasts evidence for two separate receptor types, EMBO J., 7 : 1387-1393 1988
  21. Raines, E. W. and Ross, R. : Platelet-derived growth factor I. High yield urification and evidence for multiple forms, J. Biol, Chem., 257 : 5154-5160, 1982
  22. Williams, L. T. : Signal transduction by the platelet-derived growth factor receptor, Science, 243: 1564-1570, 1987 https://doi.org/10.1126/science.2538922
  23. Hawinger, J. : Platelet secretory pathway: An overview, Method, Enzyme., 169: 191-195, 1989 https://doi.org/10.1016/0076-6879(89)69059-3
  24. Rappolee, D. A., Mark, D. and Banda, M. J. : Wound macrophages express TGF-$\alpha$ and other growth factors in vivo : Analysis of mRNA phenotyping, Science., 241: 707-712, 1988
  25. Antoniades, H. N., Galanopoulas, T. and Neville-Golden, T. : Injury induces in vivo expression of platelet-derived growth factor(PDGF) and PDGF receptor in RNA's in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts, Proc. Natl, Aca, Sci, USA., 88 : 565-569, 1991 https://doi.org/10.1073/pnas.88.2.565
  26. Sitarus, N. M., Sariban, E. and Pantagis, P. : Human iliac artery endothelial cells express both genes encoding the chains of platelet-derived growth factor (PDGF) and synthesize PDGF-like mitogen. J, Cell Physiol., 132 : 376-380, 1987 https://doi.org/10.1002/jcp.1041320228
  27. Hauschka, P. C., Mavrakos, A. E., Iafrati, M. D., Doleman, S. E. and Klagsbrun, M. : Growth factors in bone matrix, J. Biol, Chem., 261 : 12665-12674, 1986
  28. Deuel, T. F., Senior, R. M., Huang, J. S. and Griffin, G. L. : Chemotaxis of monocytes and neutrophils to platelet-derived growth factor, J. Clin.. Invest., 69: 1046-1049, 1982 https://doi.org/10.1172/JCI110509
  29. Senior, R. M., Griffin, G. L. Hwang, J. S. Walz, D. A. and Deuel, T. F. : Chemotactic activity of platelet alpha granule proteins for fibroblasts. J. Cell BioI., 96: 382-385, 1983 https://doi.org/10.1083/jcb.96.2.382
  30. Tzeng, D. Y., Deuel, T. F., Hwang, J. S. and Baehner, R. L. : Platelet-derived growth factor promotes human peripheral monocyte activation, Blood, 66 : 179-183, 1985
  31. Bauer, E. A., Cooper, T. W. Hwang, J. S., Altman, J. and Deuel, T. F. : Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor, Proc, Natl, Acad, Sci. U.S.A, 82 : 4132-4136, 1985 https://doi.org/10.1073/pnas.82.12.4132
  32. Paulsson, Y., Hammacher, A., Heldin, C. H. and Westermark, B. : Possible positive autocrine feedback in the prereplicative phase of human fibroblasts. Nature(Lond.), 328: 715-717, 1987 https://doi.org/10.1038/328715a0
  33. Blatti, S. P., Foster, D. N., Ranganathan, G., Moses, H. L. and Getz, M. J. : Induction of fibronectin gene transcription and mRNA is a primary response to growth factor stimulation of AKR-2B cells. Proc. Natl, Acad, Sci. U.S.A., 85 : 1119-1123, 1988 https://doi.org/10.1073/pnas.85.4.1119
  34. Ross, R., Glornset, J., Kariya, B. and Harker, Z. : A platelet dependent serum factor that stimulates the proliferation of atterial smooth muscle cells in vitro. Proc. Natl, Acad. Sci. U.S.A., 71 : 1207-1210, 1974 https://doi.org/10.1073/pnas.71.4.1207
  35. Kohler, N. and Lipton, A : Platelets as a source of fibroblast growth promoting activity, Exp, Cell Res, 87 : 297-301 : 1974 https://doi.org/10.1016/0014-4827(74)90484-4
  36. Pich, J. E. and Graves, D. T : Study of the growth factor requirements of human bonederived cells : a comparison with human fibroblast, Bone, 10 : 131-138, 1989 https://doi.org/10.1016/8756-3282(89)90011-2
  37. Rutherford, R. B., TrilSmith, M. D., Ryan, M. E. and Charette, M. F. : Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro, Arch, Oral Bio., 37 : 139-145, 1992 https://doi.org/10.1016/0003-9969(92)90009-W
  38. 장영명, 이만섭 : 혈소판유래성장인자가 치주조직의 재생에 미치는 영향에 관한 연구, 경희치대 논문집., 13 : 133-146, 1991
  39. 조무현, 박준봉 : 혈소판유래성장인자-BB가 성견 치근이개부병변의 조직 재생에 미치는 효과. 대한치주과학회지, 23 : 535-563, 1993
  40. Robert, A. B., Sporn, M. B., Assoian R. K., Smith, S. M., Roche, N. S., Wakefield, L. M., Heine, U. I., Liotta, L. A., Falanga, V., Kehrl, J. H. and Fauci, A. S. : Transforming growth factor type f3: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro, Proc. Natl, Acad, Sci, U.S.A., 83 : 4167-4171, 1986 https://doi.org/10.1073/pnas.83.12.4167
  41. Ignotz, R. A. and Massague, J. : Transforming growth factor $\beta$ stimulates the expression of fibroneetin and collagen and their incorporation into the extracellular matrix, J. Biol, Chem., 261 : 4337-4335, 1986
  42. Ignotz, R. A., Endo, T. and Massague, J. : Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor- $\beta$, J. BioI. Chem., 262 : 6443-6446, 1987
  43. Pfeilschifter, J., Oechsner, M., Naumann, A., Gronwald, R. G. K., Minne, H. W.. and Ziegler, R. : Stimulation of bone matrix apposition in vitro by local growth factors : a comparison between insulin-like growth factor I, plateletderived growth factor, and transforming growth factor $\beta$ Endocrinol., 127 ; 69-75, 1990 https://doi.org/10.1210/endo-127-1-69
  44. Strong, D. D., Beachler, A. L., Wergedal, J. E. and Linkhart, T. A. : insulin-like growth factor II and transforming growth factor Pregulate collagen expression in human osteoblastlike cells in vitro, J. Bone Min. Res., 6: 15-23, 1991 https://doi.org/10.1002/jbmr.5650060105
  45. Roberts, A. B. and Sporn, M. B. : TIle transforming growth factor- $\beta$s. In : Sporn, M. B. and Roberts, A. B. eds, Peptide growth factors and their receptors, Berlin, Springer-Verlag: 419-472, 1990
  46. Roberts, A. B., Frolik, C. A., Anzano, M. A. and Sporn, M. B. : Transforming growth factor from neoplastic and nonneoplastic tissues, Fed. Proc., 42: 2621-2626, 1983
  47. Overall, C. M., Wrana, J. L. and Sodek, J. : Induction of formative and resorptive cellular phenotypes in human gingival fibroblasts by transforming growth factor-$\beta$1 and concanavalin A : Regulation of matrix metalloproteinases and TIMP, J. Periodont. Res., 26: 279-282, 1991 https://doi.org/10.1111/j.1600-0765.1991.tb01658.x
  48. Overall, C. M., Wrana, J. L. and Sodek, J. : Transcriptional and post-transcriptional regulation of 72-KDa gelatinase / type IV collagenase by transforming growth factor- $\beta$1 in human fibroblasts : comparison with collagenase and tissue inhibitor of matrix metalloproteinase gene expession, J. Biol, Chem., 266 : 14064-14071, 1991
  49. Burgess, A. W. : Epidermal growth factor and transforming growth factor - alpha, In : Waterfield MD, ed, Growth factors, Br, Med, Bull., 45: 401-424, 1981
  50. Roberts, A. B., Anzano, M. A., Wakefield, L. M., Roche, N. S., Stem, D. F. and Sporn, M. B. ; Type $\beta$ transforming growth factor : A bifunctional regulator of cellular growth, Proc. Natl. Acad, Sci. U.S.A., 82: 119-123, 1985 https://doi.org/10.1073/pnas.82.1.119
  51. Derynck R : Transforming growth factor and transforming growth factor - alpha : Structure and biological activities, J. Cell Biochem., 32, 293-304, 1986 https://doi.org/10.1002/jcb.240320406
  52. Sporn, M. B., Roberts, A. B., Wakefield, L. M. and Assoian, R. K. : Transforming growth factor$\beta$: Biological function and chemical structure, Science, 233 : 532-534, 1986 https://doi.org/10.1126/science.3487831
  53. Seyedin, S. M., Thompson, A. Y. and Bertz, H. : Cartilage inducing factor : Apparent identity to transforming growth factor-$\beta$ J. Biol, Chem., 261 : 5693-5695, 1986
  54. Dennison, D. K., Vallone, D. R, Pinero, G. J., Rittman, B. and Caffesse, R G. : Differential effect of TGF -$\beta$1 and PDGF on proliferation of periodontal ligament cells and gingival fibroblasts. J, Periodontol., 65: 641-648, 1994 https://doi.org/10.1902/jop.1994.65.7.641
  55. Oates, T. W., Rouse, C. A. and Cochran, D. L. : Mitogenic effects of growth factors on human periodontal ligament cells in vitro, J. Periodontol, 64: 142-148, 1993 https://doi.org/10.1902/jop.1993.64.2.142
  56. Rizzino, A., Ruff, E. and Rizzino, H. : Induction and modulation of anchorage-independent growth by platelet-derived growth factor, fibroblast growth factor, and transforming growth factor- beta, Cancer Res., 46 : 2816-2820, 1986
  57. Ishikawa, O., LeRoy, E. C. and Trojanowska, M: Mitogenic effect of transforminggrowth factor $\beta$1 on human fibroblasts involves the induction of platelet-derived growth factor $\alpha$receptors. J. Cell Phys., 145: 181-186, 1990 https://doi.org/10.1002/jcp.1041450124
  58. Mustoe, T. A., Pierce, G. F., Thomason, A., Gramates, P., Sporn, M. B. and Deuel, T. F. : Accelerated healing of incisional wounds in rat., induced by transforming growth factor- $\beta$, Science(Wash, DC), 237 : 1333-1335, 1987 https://doi.org/10.1126/science.2442813
  59. Pierce, G. F., Mustoe, T. A., Lingelbach, J., Masakowski, V. Gramates, P, and Deuel, T. F. : Transforming growth factor $\beta$reverses the glucocorticoid- induced wound healing deficit in rats and is regulated by platelet derived growth factor in macrophages, Proc. Natl. Acad, Sci. U.S.A., 86 : 2229-2233, 1989 https://doi.org/10.1073/pnas.86.7.2229
  60. Piche, J. E., Carnes, D. L. and Graves, D. T. : Initial characterization of cells derived from human periodontia. J. Dent. Res., 68 : 761-767, 1989 https://doi.org/10.1177/00220345890680050201
  61. Peterkafsky, B. and Diegelman, R : Use of a mixture of protein free collagenases for the specific assay of radioactive collagen in the presence of other proteins, Biochemistry, 10 : 988-994, 1971 https://doi.org/10.1021/bi00782a009
  62. Peterkafsky, B and Brater, W. D. : Increased collagen synthesis in kirsten sarcoma virus transformed BALB 373 cells grown in the presence of dibutyryl cyclic AMP, Cell, # : 291-299, 1974
  63. Roberts, A. R, Anzano, M. A., Wakeftad, L. M., Roche, N. S., Stem, D. F. and Sporn, M. B. : Type $\beta$transforming growth factor: A bifunctional regulator of cellular growth, Proc. Natl, Acad. Sci., 82 : 119-123, 1985 https://doi.org/10.1073/pnas.82.1.119
  64. Sporn, M. B., Roberts, A. B., Wakefteld, L. M., and Assoian, R. K. : Transforming growth factor $\beta$: Biological function and chemical structure, Science, 233 : 532-534, 1986 https://doi.org/10.1126/science.3487831
  65. Assoian, R. K., Komoriya, O. A, Meyers, C. A., Miller, D. M. and Sporn, M. B. : Transforming growth factor-$\beta$ in human platelets, J. Biol. Chem., 258: 7155-7160, 1983
  66. Nister, M., Hammacher, A., Mellstrom, K., Siegbahn, A. Ronnstrand, A., Westermark, B. and Heidin, C. H. : A glioma-derived PDGF : A chain homodimer has different functional activities than a PDGF-AB heterodimer from human platelets, Cell, 52: 791-803, 1988 https://doi.org/10.1016/0092-8674(88)90421-7
  67. Kazlauskas, A., Bowen-Pope, D., Seifert, R., Hart, C. F. and Cooper, J. A. : Different effects of homo- and heterodimers of platelet-derived growth factor and chains on human and mouse fibroblasts, EMBO J., 7 : 3727-3731, 1988
  68. Ramakrishnan, P. R. and Cho, M. I. : Identification of platelet-derived growth factor receptors on periodontal ligament cells, J. Dent. Res., 71 : 176 Abst, No. 563, 1992
  69. Matsuda, N., Lin, W-L., Kumar, N. M., Cho, M. I. and Genco, R. J. : Mitogenic, chemotactic, and synthetic responses of rat periodontal ligament fibroblastic cells to polypeptide growth factors in vitro. J. Periodontol., 63: 515-525, 1992 https://doi.org/10.1902/jop.1992.63.6.515
  70. 조은경, 이재목, 서조영 : 변형성장인자-${\beta}_1$이 치주인대세포와 치은섬유아세포의 증식에 미치는 영향, 대한치주과학회지, 25 : 720-732, 1995
  71. 김미정, 이재목, 서조영 : 변형성장인자-$\beta$가 치주인대세포와 치은섬유아 세포의 교원질 합성능에 미치는 영향, 대한치주과학회지 출판중
  72. 오상덕, 이재목, 서조영 : 혈소판유래성장인자-BB가 치주인대세포의 세포 활성에 미치는 영향에 대한 연구, 대한치주과학회지, 24 : 303-320, 1994
  73. Canalis, E., McCarthy, T. L. and Centrella, M. : Effects of platelet-derived growth factor on bone formation in vitro, J. Cell. Physiol., 140 : 530-537, 1989 https://doi.org/10.1002/jcp.1041400319
  74. Han, E. K., Guadogno, T. M., Dalton, S. L. and Assoian, R. K. : A Cell cycle and mutational analysis of anchorage-independent growth : Cell adhesion and TGF-$\beta$, control ${G}_1$/S transit specifically, J. Cell BioI., 122: 461-471, 1993 https://doi.org/10.1083/jcb.122.2.461
  75. Pfeilshifter, J., Wolf, O., Naumann, A., Minne, H. W., Mundy, G. R. and Ziegler, R. : Chemotactic response of osteoblast-like cells to transforming growth factor-$\beta$, J. Bone. Min. Res., 5 : 825-830, 1990 https://doi.org/10.1002/jbmr.5650050805
  76. Kawamoto, T., Sato, J. D., Le, A., Polikoff, J., Sato, G. and Mendelsohn, J. : Growth stimulation of A 431 cells by epidermal growth factor : Identification of high-affinity anti-receptor monoclonal antibody, Proc. Natl, Acad. Sci. U.S.A., 80: 1337-1341, 1983 https://doi.org/10.1073/pnas.80.5.1337