Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

Abstract

A strategy for suppressing enzymes involved in inflammation could improve patient response to endodontic repair of damaged pulp tissue, report dental researchers in Korea. Direct pulp capping can preserve the health of an infected tooth, although tissue inflammation can undermine the efficacy of this intervention. Proteins known as matrix metalloproteinases (MMPs) contribute to inflammation in numerous different cell types including dental pulp. Sun-Young Kim and colleagues at Kyung Hee University identified a molecule that may limit MMPs’ effects. They found that all-trans retinoic acid (ATRA), a derivative of vitamin A, can reduce production of MMP-2 at non-toxic doses in cultured human dental pulp cells. Although ATRA did not inhibit production of MMP-9, another enzyme involved in pulp cell inflammation, follow-up experiments using inflamed as well as healthy pulp cells should help clarify ATRA’s anti-inflammatory effects.

Keywords

all-trans retinoic acid / human dental pulp cell / matrix metalloproteinase / zymography

References

[1] Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res, 2003, 92(8): 827-839.

[2] Snoek-van Beurden PA, von den Hoff JW. Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors. Biotechniques, 2005, 38(1): 73-83.

[3] Chang YC, Lai CC, Yang SF. Stimulation of matrix metalloproteinases by black-pigmented Bacteroides in human pulp and periodontal ligament cell cultures. J Endod, 2002, 28(2): 90-93.

[4] Shin SJ, Lee JI, Baek SH. Tissue levels of matrix metalloproteinases in pulps and periapical lesions. J Endod, 2002, 28(4): 313-315.

[5] Chang YC, Yang SF, Hsieh YS. Regulation of matrix metalloproteinase-2 production by cytokines and pharmacological agents in human pulp cell cultures. J Endod, 2001, 27(11): 679-682.

[6] Tsai CH, Chen YJ, Huang FM. The upregulation of matrix metalloproteinase-9 in inflamed human dental pulps. J Endod, 2005, 31(12): 860-862.

[7] Yu MK, Lee JC, Kim JH. Anti-inflammatory effect of peroxisome proliferator activated receptor gamma on human dental pulp cells. J Endod, 2009, 35(4): 524-528.

[8] Santos MC, de Souza AP, Gerlach RF. Inhibition of human pulpal gelatinases (MMP-2 and MMP-9) by zinc oxide cements. J Oral Rehabil, 2004, 31(7): 660-664.

[9] Huang FM, Yang SF, Hsieh YS. Examination of the signal transduction pathways involved in matrix metalloproteinases-2 in human pulp cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004, 97(3): 398-403.

[10] Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol, 2006, 66(7): 606-630.

[11] Thacher SM, Vasudevan J, Chandraratna RA. Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des, 2000, 6(1): 25-58.

[12] Brinckerhoff CE, McMillan RM, Dayer JM. Inhibition by retinoic acid of collagenase production in rheumatoid synovial cells. N Engl J Med, 1980, 303(8): 432-436.

[13] Bauer EA, Seltzer JL, Eisen AZ. Inhibition of collagen degradative enzymes by retinoic acid in vitro. . J Am Acad Dermatol, 1982, 6(4 Pt 2 Suppl): 603-607.

[14] Frankenberger M, Hauck RW, Frankenberger B. All trans-retinoic acid selectively down-regulates matrix metalloproteinase-9 (MMP-9) and up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) in human bronchoalveolar lavage cells. Mol Med, 2001, 7(4): 263-270.

[15] Roomi MW, Monterrey JC, Kalinovsky T. Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines. Oncol Rep, 2009, 22(6): 1283-1291.

[16] Chambaut-Guerin AM, Herigault S, Rouet-Benzineb P. Induction of matrix metalloproteinase MMP-9 (92-kDa gelatinase) by retinoic acid in human neuroblastoma SKNBE cells: relevance to neuronal differentiation. J Neurochem, 2000, 74(2): 508-517.

[17] Shibakura M, Niiya K, Kiguchi T. Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells. Br J Haematol, 2002, 118(2): 419-425.

[18] Darmanin S, Chen J, Zhao S. All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors. J Immunol, 2007, 179(7): 4616-4625.

[19] Ferreira MB, Myiagi S, Nogales CG. Time- and concentration-dependent cytotoxicity of antibiotics used in endodontic therapy. J Appl Oral Sci, 2010, 18(3): 259-263.

[20] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods, 2001, 25(4): 402-408.

[21] Nagpal S, Chandraratna RA. Vitamin A and regulation of gene expression. Curr Opin Clin Nutr Metab Care, 1998, 1(4): 341-346.

[22] Dalmolin RJ, Zanotto-Filho A, de Oliveira RB. Retinol and retinoic acid increase MMP-2 activity by different pathways in cultured Sertoli cells. Free Radic Res, 2007, 41(12): 1338-1347.

[23] Wang H, Dan Z, Jiang H. Effect of all-trans retinoic acid on liver fibrosis induced by common bile duct ligation in rats. J Huazhong Univ Sci Technol Med Sci, 2008, 28(5): 553-557.

[24] Gusman H, Santana RB, Zehnder M. Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps. Eur J Oral Sci, 2002, 110(5): 353-357.

[25] Dutta A, Sen T, Banerji A. Studies on multifunctional effect of all-trans retinoic acid (ATRA) on matrix metalloproteinase-2 (MMP-2) and its regulatory molecules in human breast cancer cells (MCF-7). J Oncol, 2009, 2009: 627840.

[26] Clark SD, Kobayashi DK, Welgus HG. Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts. J Clin Invest, 1987, 80(5): 1280-1288.