title: M2 macrophages participate in the biological tissue healing reaction to mineral trioxide aggregate.
abstract: BACKGROUND
  This study examined the protein and messenger RNA (mRNA) expression of molecules associated with M2 (wound healing) macrophages in mineral trioxide aggregate (MTA)-implanted rat subcutaneous tissue to elucidate the involvement of M2 macrophages in the connective tissue response to MTA.
  
  
  METHODS
  Silicone tubes containing freshly mixed MTA or a calcium hydroxide cement (Life; Kerr, Romulus, MI) were subcutaneously implanted into the backs of Wistar rats. Solid silicone rods implanted in different animals served as controls. The specimens were then double immunostained for ED1 (CD68, a general macrophage marker) and ED2 (CD163, an M2 macrophage marker). Immunostaining for CD34 (a marker for vascularization and wound healing) was also performed. Expression levels of CD34, CD163, and mannose receptor c type 1 (an M2 macrophage marker) mRNAs were determined with real-time polymerase chain reaction.
  
  
  RESULTS
  MTA-implanted subcutaneous tissues showed significant increases in the density of ED1+ED2+ macrophages beneath the implantation site and expression levels of CD163 and MMR mRNAs compared with Life-implanted and control tissues. MTA-implanted subcutaneous tissues also showed a significant increase of CD34-immunostained areas and up-regulation of CD34 mRNAs compared with Life-implanted and control tissues.
  
  
  CONCLUSIONS
  MTA implantation induced the accumulation of M2 macrophage marker (ED2)-expressing macrophages and enhanced the expression of M2 macrophage marker genes. MTA implantation also enhanced the expression of CD34, suggesting acceleration of the healing/tissue repair process. Taken together, biological connective tissue response to MTA may involve wound healing/tissue repair processes involving M2 macrophages.
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: tomoendo@dent.niigata-u.ac.jp.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamanaka
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shigetani
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yoshiba
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okiji
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017610:Calcium Compounds / Q000494:pharmacology*; D002126:Calcium Hydroxide / Q000494:pharmacology; D002452:Cell Count; D004338:Drug Combinations; D037181:Lectins, C-Type / Q000032:analysis; D008264:Macrophages / Q000145:classification* / Q000187:drug effects; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000032:analysis; D051116:Receptors, Scavenger / Q000032:analysis; D012387:Root Canal Filling Materials / Q000494:pharmacology*; D017640:Silicates / Q000494:pharmacology*; D040521:Subcutaneous Tissue; D014945:Wound Healing / Q000502:physiology; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D017607:Aluminum Compounds; D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D017610:Calcium Compounds; D002126:Calcium Hydroxide; D004338:Drug Combinations; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D010087:Oxides; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D012387:Root Canal Filling Materials; D017640:Silicates; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C086631:mineral trioxide aggregate
keywords: CD34; ED2; M2 macrophage; mineral trioxide aggregate; subcutaneous implantation