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| Title: | Examination of the signal transduction pathways involved in matrix metalloproteinases-2 in human pulp cells |
| Authors: | Huang, Fu-Mei
Yang, Shun-Fa
Hsieh, Yih-Shou
Liu, Chia-Ming
Yang, Li-Chiu
Chang, Yu-Chao |
| Contributors: | 中山醫學大學 |
| Date: | 2004 |
| Issue Date: | 2015-07-22T05:52:59Z (UTC)
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| ISSN: | 1079-2104 |
| Abstract: | Objectives
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.
Study design
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-κB) 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).
Conclusion
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-κB, and tyrosine kinase may be involved in the production of MMPs.
Dental pulp is of mesenchymal origin and consists of an odontoblast layer adjacent to the dentin and an immunocompetent connective tissue cover with nerves and vascular elements.1 Once the integrity of outer shield is lost, the pulp is exposed to mechanical and bacterial insults and subject to inflammation. Like any other inflammation, pulpal disease is associated with tissue degradation. At least 3 more or less interdependent pathways have been recognized in soft tissue breakdown: (1) the plasminogen-dependent pathway2. and 3.; (2) the phagocytic pathway4; and (3) the matrix metalloproteinase (MMP)-dependent pathway.5., 6. and 7.
MMPs constitute a class of structurally related proteolytic enzymes collectively responsible for the metabolism of extracellular components, including fibronectin, laminin, and proteoglycans as well as basement membrane collagens.8 Based on their substrate specificities, they can be divided into 3 subgroups: interstitial collagenase, stromelysin, and gelatinase. Two gelatinase (MMP-2 and MMP-9) are capable of degrading denatured interstitial collagens (gelatins), lamin, elastin, fibronectin, and basement membrane zone-associated collagen.9 They are involved in the normal turnover of extracellular matrix, tumor invasion, and chronic inflammatory disease.
Excess production of MMPs leads to accelerate extracellular matrix degradation associated with pathological processes such as rheumatoid arthritis, cancer, and periodontitis.10 Recently, gelatinases were found to be upregulated in inflamed pulp tissues11. and 12. and periapical lesions11 in vivo. These findings imply that dug-inhibited MMP activities may act as useful agents in pulpal/periapical therapy. Our previous studies have demonstrated that TGF-β and protein-kinase C inhibitors can inhibit MMP-2 activity in human pulp cells,5 periodontal ligament cells,7 and oral cancer cells.13 However, the signal transduction pathways seem very fruitful. The production and signal transduction pathways of MMPs still remain to be evaluated.
The fibroblast is a prominent cellular component of the dental pulp. It is believed to play an important role in extracellular matrix turnover in health and disease. MMPs play a central role in the turnover of extracellular component. During the pulpal inflammation, pulp cells have the potential to increase secretion of matrix-degrading MMPs, which in turn can destroy the extracellular matrix present in dental pulp.12 The factors or substances that can regulate MMP synthesis and secretion may be important in the pathogenesis of pulpal disease. The aim of this study was therefore to investigate the production and the signal transduction pathways involved in gelatinolytic activity in human pulp cells by using gelatin zymography. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/11535
http://dx.doi.org/10.1016/j.tripleo.2003.10.007 |
| Relation: | Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology Volume 97, Issue 3, March 2004, Pages 398–403 |
| Appears in Collections: | [生化微生物免疫研究所] 期刊論文
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