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Odontology

pp 1–9 | Cite as

ADAM28 dramatically regulates the biological features of human gingival fibroblasts

  • Zheng ZhaoEmail author
  • Jie Li
  • Xiu-Na Ding
  • Lei Zhou
  • De-Gang Sun
Original Article
  • 40 Downloads

Abstract

This study was to explore the effects of a disintegrin and metalloproteinase 28 (ADAM28) on the proliferation, differentiation, and apoptosis of human gingival fibroblasts (HGFs) and probable mechanism. After ADAM28 antisense oligodeoxynucleotide (AS-ODN) and sense oligodeoxynucleotide (S-ODN) were transfected into HGFs by Lipofectamine 2000, respectively, the expression discrepancies of ADAM28 among various groups were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western-blotting. Methabenzthiazuron (MTT) and cell-cycle assays were used to test the HGFs proliferation activity. Annexin V fluorescein isothiocyanate (FITC)/propidium iodide (PI) and alkaline phosphatase (ALP) analysis were performed separately to measure apoptosis and the cytodifferentiation standard. Immunocytochemistry and Western-blotting were carried out to determine the influence of ADAM28 AS-ODN on HGFs expressing core binding factor α1 (Cbfα1), cementum protein 1 (CEMP1), osteopontin (OPN) and dentin matrix protein 1 (DMP1). The AS-ODN group displayed the lowest expression level in HGFs, meanwhile the ADAM28 S-ODN group showed the highest. Furthermore, blocking of ADAM28 could inhibit the proliferation of HGFs, enhance HGFs differentiation and induce apoptosis of HGFs. Whereas, overexpression of ADAM28 generated the opposite effects and inhibited apoptosis. ADAM28 AS-ODN was able to notably suppress the expressions of Cbfα1 and CEMP1, and ADAM28 had positive correlations with cbfα1 and CEMP1. These provided conspicuous evidence that ADAM28 may play a crucial role in root development as a potential regulator of growth, differentiation, and apoptosis of HGFs.

Keywords

Proliferation Differentiation Apoptosis Gingival fibroblasts ADAM28 

Notes

Acknowledgements

The study was supported by a Grant from the Post-Doctoral Science Foundation Special Assistance of China (Project no. 201003774). We gratitude Dr. Hong-Jun Yang as a statistician for this paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Sawada S, Chosa N, Ishisaki A, Naruishi K. Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6. Biomed Res. 2013;34:31–40.CrossRefGoogle Scholar
  2. 2.
    Lu X, Lu D, Scully MF, Kakkar VV. Snake venom metalloproteinase containing a disintegrin-like domain, its structure-activity relationships at interacting with integrins. Curr Med Chem Cardiovasc Hematol Agents. 2005;3:249–60.CrossRefGoogle Scholar
  3. 3.
    Zhao Z, Wen LY, Jin M, Deng ZH, Jin Y. ADAM28 participates in the regulation of tooth development. Arch Oral Biol. 2006;51:996–1005.CrossRefGoogle Scholar
  4. 4.
    Apajalahti S, Hölttä P, Turtola L, Pirinen S. Prevalence of short-root anomaly in healthy young adults. Acta Odontol Scand. 2002;60:56–9.CrossRefGoogle Scholar
  5. 5.
    Bermúdez M, Imaz-Rosshandler I, Rangel-Escareño C, Zeichner-David M, Arzate H, Mercado-Celis GE. CEMP1 induces transformation in human gingival fibroblasts. PLoS One. 2015;10:0127286.Google Scholar
  6. 6.
    Zhao Z, Tang L, Deng Z, Wen L, Jin Y. Essential role of ADAM28 in regulating the proliferation and differentiation of human dental papilla mesenchymal cells hDPMCs. Histochem Cell Biol. 2008;130:1015–25.CrossRefGoogle Scholar
  7. 7.
    Wu G, Lin N, Xu L, Liu B, Feitelson MA. UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines. BMC Cancer. 2013;13:167–77.CrossRefGoogle Scholar
  8. 8.
    Zhao Z, Liu H, Wang D. ADAM28 manipulates proliferation, differentiation, and apoptosis of human dental pulp stem cells [J]. J Endod. 2011;37:332–9.CrossRefGoogle Scholar
  9. 9.
    Fourie AM, Coles F, Moreno V, Karlsson L. Catalytic activity of ADAM8, ADAM15, and MDC-l (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. J Biol Chem. 2003;278:30469–77.CrossRefGoogle Scholar
  10. 10.
    Jowett JB, Okada Y, Leedman PJ, Curran JE, Johnson MP, Moses EK. Goring HH, Mochizuki S, Blangero J, Stone L, et al. ADAM28 is elevated in humans with the metabolic syndrome and is a novel sheddase of human tumour necrosis factor-α. Immunol Cell Biol. 2012;90:966–73.CrossRefGoogle Scholar
  11. 11.
    Baurakiades E, Costa VH Jr., Raboni SM, de Almeida VR, Larsen KS, Kohler JN, Gozzo Pdo C, Klassen G, Manica GC, de Noronha L. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia. J Clin Virol. 2014;61:585–9.CrossRefGoogle Scholar
  12. 12.
    Zhang XH, Wang CC, Jiang Q, Yang SM, Jiang H, Lu J, Wang QM, Feng FE, Zhu XL, Zhao T, et al. ADAM28 overexpression regulated via the PI3K/AKT pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia. Leuk Res. 2015;15:30359–63.Google Scholar
  13. 13.
    Mitsui Y, Mochizuki S, Kodama T, Shimoda M, Ohtsuka T, Shiomi T, Chijiiwa M, Ikeda T, Kitajima M, Okada Y. ADAM28 is overexpressed in human breast carcinomas: Implications for carcinoma cell proliferation through cleavage of insulin-like growth factor binding protein-3. Cancer Res. 2006;66:9913–20.CrossRefGoogle Scholar
  14. 14.
    Wood O, Woo J, Seumois G, Savelyeva N, McCann KJ, Singh D, Jones T, Peel L, Breen M, Ward M, et al. Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors. Oncotarget. 2016;7:56781–97.CrossRefGoogle Scholar
  15. 15.
    Buckley CD, Pilling D, Lord JM, Akbar AN, Scheel-Toellner D, Salmon M. Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol. 2001;22:199–204.CrossRefGoogle Scholar
  16. 16.
    Takada H, Mihara J, Morisaki I, Hamada S. Induction of interleukin-1 and -6 in human gingival fibroblast cultures stimulated with bacteroides lipopolysaccharides. Infect Immun. 1991;59:295–301.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Slavkin HC. Antisense oligonucleotides: an experimental strategy to advance a causal analysis of development. Int J Dev Biol. 1995;39:123–6.PubMedGoogle Scholar
  18. 18.
    Santamaria D, Ortega S. Cyclins and CDKs in development and cancer: lessons from genetically modified mice. Front Biosci. 2006;11:1164–88.CrossRefGoogle Scholar
  19. 19.
    Partanen AM, Thesleff I. Growth factors and tooth development. Int J Dev Biol. 1989;33:165–72.PubMedGoogle Scholar
  20. 20.
    Cheng R, Choudhury D, Liu C, Billet S, Hu T, Bhowmick NA. Gingival fibroblasts resist apoptosis in response to oxidative stress in a model of periodontal diseases. Cell Death Discov. 2015;9:15046–56.CrossRefGoogle Scholar
  21. 21.
    Peterkova R, Peterka M, Lesot H. The developing murine dentition: a new tool for apoptosis study. Ann N Y Acad Sci. 2003;1010:453–66.CrossRefGoogle Scholar
  22. 22.
    Vaahtokari A, Aberg T, Thesleff I. Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4. Development. 1996;122:121–9.PubMedGoogle Scholar
  23. 23.
    Bolean M, Simão AMS, Barioni MB, Favarin BZ, Sebinelli HG, Veschi EA, Janku TAB, Bottini M, Hoylaerts MF, Itri R, Millán JL, Ciancaglini P. Biophysical aspects of biomineralization. Biophys Rev. 2017;9:747–60.CrossRefGoogle Scholar
  24. 24.
    Unda FJ, Martin A, Hernandez C, Perez-Nanclares G, Hilario E, Arechaga J. FGFs-1 and -2, and TGFb1 as inductive signals modulating in vitro odontoblast differentiation. Adv Dent Res. 2001;15:34–7.CrossRefGoogle Scholar
  25. 25.
    Shiba H, Mouri Y, Komatsuzawa H, Mizuno N, Xu W, Noguchi T, et al. Enhancement of alkaline phosphatase synthesis in pulp cells co-cultured with epithelial cells derived from lower rabbit incisors. Cell Biol Int. 2003;27:815–23.CrossRefGoogle Scholar
  26. 26.
    Zhu L, Skoultchi AI. Coordinating cell proliferation and differentiation. Curr Opin Genet Dev. 2001;11:91–7.CrossRefGoogle Scholar
  27. 27.
    Kobayashi I, Kiyoshima T, Wada H, Matsuo K, Nonaka K, Honda JY, et al. Type II/III Runx2/Cbfα1 is required for tooth germ development. Bone. 2006;38:836–44.CrossRefGoogle Scholar
  28. 28.
    Kitagawa M, Tahara H, Kitagawa S, Oka H, Kudo Y, Sato S, et al. Characterization of established cementoblasts-like cells from human cementum-lining cells in vitro and in vivo. Bone. 2006;39:1035–42.CrossRefGoogle Scholar
  29. 29.
    Arzate HJ, Chimal-Monroy L, Hernández-Lagunas L. Díaz de León. Human cementum protein extract promotes chondrogenesis and mineralization in mesenchymal cells. J Periodont Res. 1996;31:144–8.CrossRefGoogle Scholar
  30. 30.
    Alvarez Pérez MA, Pitaru S, Alvarez Fregoso O, Reyes Gasga J, Arzate H. Anti-cementoblastoma-derived protein antibody partially inhibits mineralization on a cementoblastic cell line. J Struct Biol. 2003;143:1–13.CrossRefGoogle Scholar
  31. 31.
    Carmona-Rodríguez B, Alvarez-Pérez MA, Narayanan AS, Zeichner-David M, Reyes-Gasga J, Molina-Guarneros J, et al. Human cementum protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts. Biochem Biophys Res Commun. 2007;358:763–9.CrossRefGoogle Scholar
  32. 32.
    Zhao Z, Liu H, Wang D. ADAM28 manipulates proliferation, differentiation, and apoptosis of human dental pulp stem cells. J Endod. 2011;37:332–9.CrossRefGoogle Scholar
  33. 33.
    Herat L, Rudnicka C, Okada Y, Mochizuki S, Schlaich M, Matthews V. The metalloproteinase ADAM28 promotes metabolic dysfunction in mice. Int J Mol Sci. 2017;18:263–73.CrossRefGoogle Scholar
  34. 34.
    Mochizuki S, Shimoda M, Shiomi T, Fujii Y, Okada Y. ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3. Biochem Biophys Res Commun. 2004;315:79–84.CrossRefGoogle Scholar
  35. 35.
    Shalhoub V, Aslam F, Breen E, Van Wijnen A, Bortell R, Stein GS, et al. Multiple levels of steroid hormone-dependent control of osteocalcin during osteoblast differentiation: glucocorticoid regulation of basal and vitamin D stimulated gene expression. J Cell Biochem. 1998;69:154–68.CrossRefGoogle Scholar
  36. 36.
    Qin C, D’Souza R, Feng JQ. Dentin matrix protein 1 (DMP1): new and important roles for biomineralization and phosphate homeostasis. J Dent Res. 2007;86:1134–41.CrossRefGoogle Scholar

Copyright information

© The Society of The Nippon Dental University 2018

Authors and Affiliations

  • Zheng Zhao
    • 1
    Email author
  • Jie Li
    • 1
  • Xiu-Na Ding
    • 1
  • Lei Zhou
    • 1
  • De-Gang Sun
    • 1
  1. 1.Qingdao Stomatological HospitalQingdaoPeople’s Republic of China

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