Examination of the signal transduction pathways involved in matrix metalloproteinases-2 in human pulp cells.
OBJECTIVE
Matrix metalloproteinases (MMPs) play an important role in pulp tissue destruction. However, the mechanisms and signal transduction pathways involved in the production of MMPs in human pulp cells are not fully understood. The purpose of this study was to investigate the gelatinolytic activity in human pulp cells stimulated with various pharmacological agents.


METHODS
Human dental pulp cells were cultured using an explant technique obtained from impacted third molars with informed consent of the patients. The effects of p38 inhibitor SB203580, MEK inhibitor U0126, extracellular signal-regulated kinase (ERK) inhibitor PD098059, phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 (COX-2) inhibitor NS-398, nuclear factor kappa B (NF-kappaB) inhibitor dexamethasone, and tyrosine kinase inhibitor herbimycin A on the production and secretion of MMPs by human pulp cells were determined by gelatin zymography.


RESULTS
The main gelatinase secreted by human pulp cells migrated at 72 kd and represented MMP-2. Minor gelatinolytic bands were also observed at 92 kd regions that correspond to MMP-9. After a 4-day culture period, NS-398, dexamethasone, and herbimycin A were found to depress MMP-2 production (P<.05). The inhibition decreased in an order of dexamethasone >NS-398>herbimycin A. Human pulp cells, however, treated with various pharmacological agents had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions (P>.05).


CONCLUSIONS
These observations suggest that NS-398, dexamethasone, and herbimycin A can regulate MMP-2 produced by human pulp cells. The signal transduction pathways COX-2, NF-kappaB, and tyrosine kinase may be involved in the production of MMPs.
Huang
Fu-Mei
FM
School of Dentistry, Oral Medicine Center, Chung Shan Medical University Hospital, Taiwan.
Yang
Shun-Fa
SF
Hsieh
Yih-Shou
YS
Liu
Chia-Ming
CM
Yang
Li-Chiu
LC
Chang
Yu-Chao
YC
D016227:Benzoquinones; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003782:Dental Pulp / Q000201:enzymology*; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D047029:Lactams, Macrocyclic; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D016227:Benzoquinones; D002070:Butadienes; D002867:Chromones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D009025:Morpholines; D016328:NF-kappa B; D009570:Nitriles; D009578:Nitrobenzenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D011809:Quinones; D013449:Sulfonamides; C113580:U 0126; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017828:Rifabutin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C020754:herbimycin; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one