title: MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration.
abstract: Matrix metalloproteinase-3 (MMP-3) expression is promoted after pulpotomy, and application of MMP-3 to dental pulp after pulpotomy accelerates angiogenesis and hard tissue formation. However, the mechanism by which MMP-3 promotes dental pulp wound healing is still unclear. Connective tissue growth factor/CCN family 2 (CTGF/CCN2), a protein belonging to the CCN family, is considered to participate in wound healing, angiogenesis, and cell migration. In this study, we examined the involvement of CTGF/CCN2 in MMP-3-induced cell migration in human dental pulp (fibroblast-like) cells. In human dental pulp cells, MMP-3 promoted cell migration, but this effect was clearly blocked in the presence of anti-CTGF/CCN2 antibody. MMP-3 provoked mRNA and protein expression and secretion of CTGF/CCN2 in a concentration- and time-dependent manner. The MMP-3 inhibitor NNGH failed to suppress MMP-3-induced CTGF/CCN2 protein expression. The potent dynamin inhibitor dynasore clearly inhibited MMP-3-induced CTGF/CCN2 expression. These results strongly suggest that MMP-3 induces CTGF/CCN2 production independently of the protease activity of MMP-3 and dependently on dynamin-related endocytosis, which is involved in cell migration in human dental pulp cells.
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan. mako08014@g.nihon-u.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Muromachi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kamio
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.forename: Motoyo
authors.initials: M
authors.lastname: Annen-Kamio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D003782:Dental Pulp / Q000166:cytology*; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C526317:CCN2 protein, human; D017931:DNA Primers; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D019278:Matrix Metalloproteinase 3; D034281:Dynamins