Advertisement

Histochemistry and Cell Biology

, Volume 142, Issue 3, pp 297–305 | Cite as

Perlecan-enriched intercellular space of junctional epithelium provides primary infrastructure for leukocyte migration through squamous epithelial cells

  • Satoshi Maruyama
  • Manami Itagaki
  • Hiroko Ida-Yonemochi
  • Takehiko Kubota
  • Manabu Yamazaki
  • Tatsuya Abé
  • Hiromasa Yoshie
  • Jun Cheng
  • Takashi SakuEmail author
Original Paper

Abstract

The aim of this study was to demonstrate the presence of intraepithelial stroma represented by extracellular matrix (ECM) deposits in the junctional epithelium to clarify its function as a scaffold for leukocyte migration through epithelial cells. Twenty-three biopsy specimens from the gingiva including the junctional epithelium were examined to determine comparative protein and gene level expression profiles for keratin and ECM molecules between the junctional epithelium and the gingival epithelium using immunohistochemistry and in situ hybridization. Intraepithelial leukocyte types and frequencies were also determined and compared between the junctional and gingival epithelia. In the junctional epithelium, which was positive for keratin 19, perlecan was strongly deposited in intercellular space of the whole epithelial layer, while it was faintly positive around the parabasal layer of the gingival epithelium. Perlecan mRNA signals were enhanced to a greater degree in both epithelial and inflammatory cells within the junctional epithelium. In the junctional epithelium, greater numbers of neutrophils and macrophages were found as compared with the gingival epithelium. Our results showed that perlecan is the primary ECM molecule comprising intraepithelial stroma of the junctional epithelium, in which leukocytes may migrate on ECM scaffolds in intercellular space toward the surface of the gingival sulci or pockets.

Keywords

Junctional epithelium Gingival epithelium Intercellular space Intraepithelial stroma Perlecan Leukocyte migration 

Notes

Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.

Conflict of interest

The authors have no conflict of interest to declare.

References

  1. Abe Y, Hara T, Saku T, Kato I (1994) Immunohistological study of cytokeratin 19 expression in regenerated junctional epithelium of rats. J Periodontal Res 29:418–420PubMedGoogle Scholar
  2. Ahsan MS, Yamazaki M, Maruyama S, Kobayashi T, Ida-Yonemochi H, Hasegawa M, Ademola AH, Cheng J, Saku T (2011) Differential expression of perlecan receptors, α-dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma. J Oral Pathol Med 40:552–559Google Scholar
  3. Alvarado CG, Maruyama S, Cheng J, Ida-Yonemochi H, Kobayashi T, Yamazaki M, Takagi R, Saku T (2011) Nuclear translocation of beta-catenin synchronized with loss of E-cadherin in oral epithelial dysplasia with a characteristic two-phase appearance. Histopathology 59:283–291PubMedGoogle Scholar
  4. Bampton JL, Shirlaw PJ, Topley S, Weller P, Wilton JM (1991) Human junctional epithelium: demonstration of a new marker, its growth in vitro and characterization by lectin reactivity and keratin expression. J Investig Dermatol 96:708–717PubMedGoogle Scholar
  5. Bosshardt DD, Lang NP (2005) The junctional epithelium: from health to disease. J Dent Res 84:9–20PubMedGoogle Scholar
  6. Cheng J, Irié T, Munakata R, Kimura S, Nakamura H, He RG, Lui AR, Saku T (1995) Biosynthesis of basement membrane molecules by salivary adenoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study. Virchows Arch 426:577–586Google Scholar
  7. Datta S, Pierce M, Datta MW (2006) Perlecan signaling: helping hedgehog stimulate prostate cancer growth. Int J Biochem Cell Biol 38:1855–1861PubMedGoogle Scholar
  8. Farach-Carson MC, Warren CR, Harrington DA, Carson DD (2013) Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders. Matrix Biol. doi:  10.1016/j.matbio.2013.08.004. [Epub ahead of print]
  9. Feghali-Assaly M, Sawaf MH, Serres G, Forest N, Ouhayoun JP (1994) Cytokeratin profile of the junctional epithelium in partially erupted teeth. J Periodontal Res 29:185–195PubMedGoogle Scholar
  10. Feghali-Assaly M, Sawaf MH, Ouhayoun JP (1997) In situ hybridization study of cytokeratin 4, 13, 16 and 19 mRNAs in human developing junctional epithelium. Eur J Oral Sci 105:599–608PubMedGoogle Scholar
  11. Gratchev A, Guillot P, Hakiy N, Politz O, Orfanos CE, Schledzewski K, Goerdt S (2001) Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein betaIG-H3. Scand J Immunol 53:386–392PubMedGoogle Scholar
  12. Hatakeyama S, Yaegashi T, Oikawa Y, Fujiwara H, Mikami T, Takeda Y, Satoh M (2006) Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia. J Periodontal Res 41:322–328PubMedGoogle Scholar
  13. Hormia M, Sahlberg C, Thesleff I, Airenne T (1998) The epithelium-tooth interface—a basal lamina rich in laminin-5 and lacking other known laminin isoforms. J Dent Res 77:1479–1485PubMedGoogle Scholar
  14. Hormia M, Owaribe K, Virtanen I (2001) The dento-epithelial junction: cell adhesion by type I hemidesmosomes in the absence of a true basal lamina. J Periodontol 72:788–797PubMedGoogle Scholar
  15. Ida-Yonemochi H (2013) Role of perlecan, a basement membrane-type heparan sulfate proteoglycan, in enamel organ morphogenesis. J Oral Biosci 55:23–28Google Scholar
  16. Ida-Yonemochi H, Ikarashi T, Nagata M, Hoshina H, Takagi R, Saku T (2002) The basement membrane type heparan sulfate proteoglycan (perlecan) in ameloblastomas: its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells. Virchows Arch 441:165–173Google Scholar
  17. Ida-Yonemochi H, Ohshiro K, Swelam W, Metwaly H, Saku T (2005) Perlecan, a basement membrane type heparan sulfate proteoglycan, in the enamel organ: its intraepithelial localization in the stellate reticulum. J Histochem Cytochem 53:763–772Google Scholar
  18. Ida-Yonemochi H, Nakajima M, Saku T (2010) Heparanase, heparan sulfate and perlecan distribution along with the vascular penetration during stellate reticulum retraction in the mouse enamel organ. Arch Oral Biol 55:778–787PubMedGoogle Scholar
  19. Ida-Yonemochi H, Ahsan MS, Saku T (2011a) Differential expression profiles between α-dystroglycan and integrin β1 in ameloblastoma: two possible perlecan signaling pathways for cellular growth and differentiation. Histopathology 58:234–245PubMedGoogle Scholar
  20. Ida-Yonemochi H, Satokata I, Ohshima H, Sato T, Yokoyama M, Yamada Y, Saku T (2011b) Morphogenetic roles of perlecan in the tooth enamel organ: an analysis of overexpression using transgenic mice. Matrix Biol 30:379–388PubMedGoogle Scholar
  21. Ida-Yonemochi H, Harada H, Ohshima H, Saku T (2013) Reciprocal expressions between α-dystroglycan and integrin β1, perlecan receptors, in the murine enamel organ development. Gene Expr Patterns 13:293–302PubMedGoogle Scholar
  22. Ikarashi T, Ida-Yonemochi H, Ohshiro K, Cheng J, Saku T (2004) Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium. J Oral Pathol Med 33:87–95PubMedGoogle Scholar
  23. Iozzo RV (2005) Basement membrane proteoglycans: from cellar to ceiling. Nat Rev Mol Cell Biol 6:646–656PubMedGoogle Scholar
  24. Iozzo RV, Cohen IR, Grässel S, Murdoch AD (1994) The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J 302:625–639PubMedCentralPubMedGoogle Scholar
  25. Kaplan GB, Pameijer CH, Ruben MP (1977) Scanning electron microscopy of sulcular and junctional epithelia correlated with histology (part 1). J Periodontol 48:446–451PubMedGoogle Scholar
  26. Kimura S, Cheng J, Toyoshima K, Oda K, Saku T (1999) Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC3, adenoid cystic carcinoma cells of human salivary gland origin. J Biochem 125:406–413PubMedGoogle Scholar
  27. Kinumatsu T, Hashimoto S, Muramatsu T, Sasaki H, Jung HS, Yamada S, Shimono M (2009) Involvement of laminin and integrins in adhesion and migration of junctional epithelium cells. J Periodontal Res 44:13–20PubMedGoogle Scholar
  28. Kobayashi T, Maruyama S, Cheng J, Ida-Yonemochi H, Yagi M, Takagi R, Saku T (2010) Histopathological varieties of oral carcinoma in situ: diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia. Pathol Int 60:154–164Google Scholar
  29. Kobayashi T, Maruyama S, Abé T, Cheng J, Takagi R, Saito C, Saku T (2012) Keratin-10-positive orthokeratotic dysplasia: a new leukoplakia-type precancerous entity of the oral mucosa. Histopathology 61:910–920Google Scholar
  30. Kutys ML, Doyle AD, Yamada KM (2013) Regulation of cell adhesion and migration by cell-derived matrices. Exp Cell Res 319:2434–2439PubMedGoogle Scholar
  31. Larjava H, Koivisto L, Häkkinen L, Heino J (2011) Epithelial integrins with special reference to oral epithelia. J Dent Res 90:1367–1376PubMedCentralPubMedGoogle Scholar
  32. Mackenzie IC, Gao Z (1993) Patterns of cytokeratin expression in the epithelia of inflamed human gingiva and periodontal pockets. J Periodontal Res 28:49–59PubMedGoogle Scholar
  33. Maruyama S, Cheng J, Yamazaki M, Liu A, Saku T (2009) Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas. J Oral Pathol Med 38:377–385PubMedGoogle Scholar
  34. Massoth DL, Dale BA (1986) Immunohistochemical study of structural proteins in developing junctional epithelium. J Periodontol 57:756–763PubMedGoogle Scholar
  35. Metwaly H, Cheng J, Ida-Yonemochi H, Ohshiro K, Jen KY, Liu AR, Saku T (2003) Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion). Virchows Arch 443:17–27Google Scholar
  36. Metwaly H, Maruyama S, Yamazaki M, Tsuneki M, Abé T, Jen KY, Cheng J, Saku T (2012) Parenchymal-stromal switching for extracellular matrix production on invasion of oral squamous cell carcinoma. Hum Pathol 43:1973–1981PubMedGoogle Scholar
  37. Mikami T, Cheng J, Maruyama S, Kobayashi T, Funayama A, Yamazaki M, Adeola HA, Wu L, Shingaki S, Saito C, Saku T (2011) Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ. Oral Oncol 47:497–503PubMedGoogle Scholar
  38. Murata M, Hara K, Saku T (1997) Dynamic distribution of fibroblast growth factor during epulis formation. J Oral Pathol Med 26:224–232PubMedGoogle Scholar
  39. Nagarakanti S, Ramya S, Babu P, Arun KV, Sudarsan S (2007) Differential expression of E-cadherin and cytokeratin 19 and net proliferative rate of gingival keratinocytes in oral epithelium in periodontal health and disease. J Periodontol 78:2197–2202PubMedGoogle Scholar
  40. Oksonen J, Sorokin LM, Virtanen I, Hormia M (2001) The junctional epithelium around murine teeth differs from gingival epithelium in its basement membrane composition. J Dent Res 80:2093–2097PubMedGoogle Scholar
  41. Okuda K, Murata M, Sugimoto M, Saito Y, Kabasawa Y, Yoshie H, Saku T, Hara K (1998) TGF-β1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodeling by extracellular matrix molecules and PCNA. J Oral Pathol Med 27:463–469PubMedGoogle Scholar
  42. Pritlove-Carson S, Charlesworth S, Morgan PR, Palmer RM (1997) Cytokeratin phenotypes at the dento-gingival junction in relative health and inflammation, in smokers and nonsmokers. Oral Dis 3:19–24PubMedGoogle Scholar
  43. Saku T, Furthmayr H (1989) Characterization of the major heparan sulfate proteoglycan secreted by bovine aortic endothelial cells in culture. Homology to the large molecular weight molecule of basement membranes. J Biol Chem 264:3514–3523PubMedGoogle Scholar
  44. Schroeder HE, Listgarten MA (2003) The junctional epithelium: from strength to defense. J Dent Res 82:158–161PubMedGoogle Scholar
  45. Syafriadi M, Cheng J, Jen KY, Ida-Yonemochi H, Suzuki M, Saku T (2005) Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells. J Oral Pathol Med 34:140–149PubMedGoogle Scholar
  46. Tilakaratne WM, Kobayashi T, Ida-Yonemochi H, Swelam W, Yamazaki M, Mikami T, Alvarado CG, Shahidul AM, Maruyama S, Cheng J, Saku T (2009) Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ: an aid for histopathologic recognition of their cell proliferation centers. J Oral Pathol Med 38:348–355PubMedGoogle Scholar
  47. Tsuneki M, Cheng J, Maruyama S, Ida-Yonemochi H, Nakajima M, Saku T (2008) Perlecan-rich epithelial linings as a background of proliferative potentials of keratocystic odontogenic tumor. J Oral Pathol Med 37:287–293PubMedGoogle Scholar
  48. Utsunomiya H, Tilakaratne WM, Oshiro K, Maruyama S, Suzuki M, Ida-Yonemochi H, Cheng J, Saku T (2005) Extracellular matrix remodeling in oral submucous fibrosis its stage-specific modes revealed by immunohistochemistry and in situ hybridization. J Oral Pathol Med 34:498–507PubMedGoogle Scholar
  49. Whitelock JM, Melrose J, Iozzo RV (2008) Diverse cell signaling events modulated by perlecan. Biochemistry 47:11174–11183PubMedCentralPubMedGoogle Scholar
  50. Zhang J, Wang Y, Chu Y, Su L, Gong Y, Zhang R, Xiong S (2006) Agrin is involved in lymphocytes activation that is mediated by alpha-dystroglycan. FASEB J 20:50–58PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Satoshi Maruyama
    • 1
    • 2
  • Manami Itagaki
    • 2
    • 3
  • Hiroko Ida-Yonemochi
    • 1
    • 2
    • 4
  • Takehiko Kubota
    • 3
  • Manabu Yamazaki
    • 2
  • Tatsuya Abé
    • 1
    • 2
  • Hiromasa Yoshie
    • 3
  • Jun Cheng
    • 2
  • Takashi Saku
    • 1
    • 2
    Email author
  1. 1.Oral Pathology Section, Department of Surgical PathologyNiigata University HospitalNiigataJapan
  2. 2.Division of Oral Pathology, Department of Tissue Regeneration and ReconstructionNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  3. 3.Division of Periodontology, Department of Oral Biological ScienceNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  4. 4.Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and ReconstructionNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

Personalised recommendations