Apoptosis of oral epithelial cells in oral lichen planus caused by upregulation of BMP-4

S. G. Kim, C. H. Chae, B. O. Cho, H. N. Kim, H. J. Kim, In-San Kim, J. Y. Choi

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Abstract

BACKGROUND: Bone morphogenic protein (BMP-4) is a member of transforming growth factor (TGF-β) family and involved in various functions including apoptosis during neural ectoderm development. The objective of this study is to determine whether BMP-4 is involved in apoptosis, one characteristic, of human oral lichen planus (OLP). METHODS: Immunohistochemistry and in situ hybridization for BMP-4 were carried out in OLP (n = 21) and normal human oral mucosa (NOM, n = 31). Five tissue samples from NOM and OLP were underwent reverse transcriptase-polymerase chain reaction (RT-PCR). In vitro organ culture of oral mucosa was carried out with beads soaked with various concentration of BMP-4 (0.1, 1, and 10 μg/ml). The samples from in vitro organ culture were undergone haematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling technique (TUNEL) assay, and immunohistochemical study with p53, matrix metalloproteinases q3(MMP)-1, and MMP-3. Involucrin expression was determined by western blot analysis after treatment with BMP-4 or TGF-β1 on human oral keratinocytes. RESULTS: In immunohistochemical analysis, expression of BMP-4 was higher in OLP than NOM. BMP-4 mRNA expression was also detected in epithelial cells of both NOM and OLP together with underlying T-lymphocytes by in situ hybridization and RT-PCR. In oral mucosa organ culture, BMP-4 soaked beads induced apoptosis of epithelial cells. Acantolysis combined with apoptosis in oral epithelium was observed at 1 μg/ml of BMP-4 beads and it was due in part to the induction of p53 and MMP-1. Even MMP-3 induction was found in lower concentration of BMP-4 (0.1 and 1 μg/ml). Moreover, the expression of MMP-1 and MMP-3 was also observed in OLP. Recombinant BMP-4 or TGF-β1 increased involucrin expression in human oral keratinocytes cell line. CONCLUSIONS: Expression of BMP-4 of epithelial cells was higher in OLP than NOM. High concentration of BMP-4 caused an apoptosis of oral epithelial cells in oral mucosa organ culture. Therefore, over-expression of BMP-4 is one causing factor for apoptosis of oral epithelial cells through upregulation of p53, MMP1 and MMP3 in OLP.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalJournal of Oral Pathology and Medicine
Volume35
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1
Externally publishedYes

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Keywords

  • Apoptosis
  • BMP-4
  • Oral lichen planus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oral Surgery
  • Otorhinolaryngology
  • Cancer Research
  • Periodontics

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