title: CCN2/CTGF expression via cellular uptake of BMP-1 is associated with reparative dentinogenesis.
abstract: OBJECTIVE
  CCN family member 2/connective tissue growth factor (CCN2/CTGF) is known as an osteogenesis-related molecule and is thought to be implicated in tooth growth. Bone morphogenetic protein-1 (BMP-1) contributes to tooth development by the degradation of dentin-specific substrates as a metalloprotease. In this study, we demonstrated the correlations between CCN2/CTGF and BMP-1 in human carious teeth and the subcellular dynamics of BMP-1 in human dental pulp cells.
  
  
  METHODS
  Expression of CCN2/CTGF and BMP-1 in human carious teeth was analyzed by immunohistochemistry. BMP-1-induced CCN2/CTGF protein expression in primary cultures of human dental pulp cells was observed by immunoblotting. Intracellular dynamics of exogenously administered fluorescence-labeled BMP-1 were observed using confocal microscope.
  
  
  RESULTS
  Immunoreactivities for CCN2/CTGF and BMP-1 were increased in odontoblast-like cells and reparative dentin-subjacent dental caries. BMP-1 induced the expression of CCN2/CTGF independently of protease activity in the cells but not that of dentin sialophosphoprotein (DSPP) or dentin matrix protein-1 (DMP-1). Exogenously added BMP-1 was internalized into the cytoplasm, and the potent dynamin inhibitor dynasore clearly suppressed the BMP-1-induced CCN2/CTGF expression in the cells.
  
  
  CONCLUSIONS
  CCN2/CTGF and BMP-1 coexist beneath caries lesion and CCN2/CTGF expression is regulated by dynamin-related cellular uptake of BMP-1, which suggests a novel property of metalloprotease in reparative dentinogenesis.
authors.affiliation: Department of Pulp Biology and Endodontics, Kanagawa Dental University, Yokosuka, Kanagawa, Japan.|Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Muromachi
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kamio
authors.affiliation: Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuki-Fukushima
authors.affiliation: Department of Oral Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Pulp Biology and Endodontics, Kanagawa Dental University, Yokosuka, Kanagawa, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tani-Ishii
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugiya
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.|Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D055395:Bone Morphogenetic Protein 1 / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D055513:Connective Tissue Growth Factor / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D003731:Dental Caries / Q000378:metabolism; D003782:Dental Pulp / Q000378:metabolism*; D003804:Dentin / Q000737:chemistry; D003810:Dentinogenesis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D061251:Primary Cell Culture; D012795:Sialoglycoproteins / Q000378:metabolism; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
chemical_list: D055395:Bone Morphogenetic Protein 1; D055513:Connective Tissue Growth Factor; D016326:Extracellular Matrix Proteins; D006835:Hydrazones; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C526317:CCN2 protein, human; C513309:DMP1 protein, human; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; C525705:BMP1 protein, human
keywords: BMP-1; CCN2/CTGF; Endocytosis; dental pulp; reparative dentinogenesis