title: Midkine expression in human periapical granulomas.
abstract: BACKGROUND
  The expression of midkine (MK), a heparin-binding growth factor, is increased in various human tumors, making it a promising tumor marker and target for tumor therapy. MK is also related to the regulation of the development and etiology of chronic or autoimmune diseases; however, the involvement of MK in apical periodontitis has never been examined. This study compared the localization of MK-expressing cells and MK messenger RNA expression in periapical granulomas with healthy gingival tissues.
  
  
  METHODS
  Periapical lesions were removed surgically from chronic apical periodontitis patients, and serial tissue sections were stained with hematoxylin-eosin. The lesions diagnosed as periapical granulomas pathologically were examined by immunohistochemistry using human MK monoclonal antibodies. MK messenger RNA expression was also detected using real-time polymerase chain reaction analysis. Healthy gingival tissues were analyzed in the same manner.
  
  
  RESULTS
  MK was expressed by inflammatory cells, such as macrophages, lymphocytes, and neutrophils, as well as by endothelial cells in periapical granulomas but not in healthy gingival tissues. The MK-expressing inflammatory cells were seen adjacent to blood vessels, which contained MK-expressing endothelial cells, suggesting the interaction of MK among these cells during the process of inflammatory cell infiltration. Quantitative analysis of MK messenger RNA expression revealed that periapical granulomas expressed significantly more MK than healthy gingival tissues.
  
  
  CONCLUSIONS
  These findings suggest that MK is involved in the pathogenesis of periapical granulomas.
authors.affiliation: Nihon University Graduate School of Dentistry, Nihon, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hatori
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeichi
authors.forename: Bunnai
authors.initials: B
authors.lastname: Ogiso
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000032:analysis* / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D010484:Periapical Granuloma / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D000078792:Midkine