Effects of hyaluronan oligosaccharide on the expression of MMP-1 in periodontal ligament cells.
It is well known that low-molecular weight hyaluronan (HA) is detected in human periodontal tissue under inflammatory conditions. HA oligosaccharide (HAoligo) has been demonstrated to induce matrix metalloproteinase (MMP)-1 expression in dendritic cells and chondrocytes, however, the bioactivities of HAoligo in periodontal ligament (PDL) cells remain unclear. In this study, we investigated the effect of HAoligo on MMP-1 expression in human PDL (HPDL) cells and the mechanisms in terms of the signal transmission. HAoligo was generated and purified from commercial human umbilical cord HA. HPDL cells were isolated from healthy ligaments, and cultured with HAoligo for 0-24h. The expression of MMP-1, tissue inhibitor of MMPs (TIMP)-1 and TIMP-2 was analyzed by real-time PCR and Western blot analyses. Effects of specific inhibitors of p38 mitogen-activated protein kinase (MAPK) activity, MAPK kinase activity and NFkB activity on HAoligo-induced MMP-1 expression in HPDL cells were also investigated by real-time PCR and Western blot analyses. HAoligo remarkably enhanced MMP-1 expression in both mRNA and protein levels, but no effect was shown on the expression of TIMP-1 and TIMP-2 mRNAs. Inhibition of p38MAPK activity decreased the MMP-1 expression. Neither inhibition of NFkB nor MAPKK activity affected the MMP-1 expression. It was suggested that HAoligo induces MMP-1 expression in HPDL cells, and p38MAPK plays a crucial role in signal transduction for MMP-1 inducted by HAoligo.
Nakatani
Yuki
Y
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Tanimoto
Kotaro
K
Tanaka
Nobuaki
N
Tanne
Yuki
Y
Kamiya
Takashi
T
Kunimatsu
Ryo
R
Tanaka
Eiji
E
Tanne
Kazuo
K
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects; D009844:Oligosaccharides / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000187:drug effects; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016328:NF-kappa B; D009844:Oligosaccharides; D011725:Pyridines; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C001329:helenalin; D006820:Hyaluronic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one