DOI QR코드

DOI QR Code

Assessment of MMP-1, MMP-8 and TIMP-2 in experimental periodontitis treated with kaempferol

  • Balli, Umut (Department of Periodontology, Bulent Ecevit University Faculty of Dentistry) ;
  • Cetinkaya, Burcu Ozkan (Department of Periodontology, Ondokuzmayis University Faculty of Dentistry) ;
  • Keles, Gonca Cayir (Department of Periodontology, Ondokuzmayis University Faculty of Dentistry) ;
  • Keles, Zeynep Pinar (Department of Periodontology, Ondokuzmayis University Faculty of Dentistry) ;
  • Guler, Sevki (Department of Periodontology, Ondokuzmayis University Faculty of Dentistry) ;
  • Sogut, Mehtap Unlu (Ondokuzmayis University Samsun High School of Health) ;
  • Erisgin, Zuleyha (Department of Histology and Embryology, Giresun University Faculty of Medicine)
  • Received : 2015.12.21
  • Accepted : 2016.02.28
  • Published : 2016.04.30

Abstract

Purpose: The objective of this study was to investigate the effect of a dietary flavonoid, kaempferol, which has been shown to possess antiallergic, anti-inflammatory, anticarcinogenic, and antioxidant activities on the periodontium by histomorphometric analysis and on gingival tissue matrix metalloproteinase-1 (MMP-1), MMP-8, and tissue inhibitor of metalloproteinase-2 (TIMP-2) by biochemical analysis of rats after experimental periodontitis induction. Methods: Sixty Wistar rats were randomly divided into six groups of ten rats each, and silk ligatures were placed around the cervical area of the mandibular first molars for 15 days, except in the healthy control rats. In the experimental periodontitis groups, systemic kaempferol (10 mg/kg/2d) and saline were administered by oral gavage at two different periods (with and without the presence of dental biofilm) to all rats except for the ten non-medicated rats. Alveolar bone area, alveolar bone level, and attachment level were determined by histomorphometric analysis, and gingival tissue levels of MMP-1, MMP-8, and TIMP-2 were detected by biochemical analysis. Results: Significantly greater bone area and significantly less alveolar bone and attachment loss were observed in the kaempferol application groups compared to the control groups (P<0.05). In addition, gingival tissue MMP-1 and -8 levels were significantly lower in the kaempferol application groups compared to the control groups and the periodontitis group (P<0.001). There were no statistically significant differences in TIMP-2 levels between the kaempferol and saline application groups (P>0.05). Conclusions: Kaempferol application may be useful in decreasing alveolar bone resorption, attachment loss, and MMP-1 and -8 production in experimental periodontitis.

Keywords

References

  1. Giannobile WV. Host-response therapeutics for periodontal diseases. J Periodontol 2008;79 Suppl:1592-600. https://doi.org/10.1902/jop.2008.080174
  2. Bascones-Martinez A, Munoz-Corcuera M, Noronha S, Mota P, Bascones-Ilundain C, Campo-Trapero J. Host defence mechanisms against bacterial aggression in periodontal disease: Basic mechanisms. Med Oral Patol Oral Cir Bucal 2009;14:e680-5.
  3. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000 1997;14:9-11. https://doi.org/10.1111/j.1600-0757.1997.tb00189.x
  4. Page RC. Milestones in periodontal research and the remaining critical issues. J Periodontal Res 1999;34:331-9. https://doi.org/10.1111/j.1600-0765.1999.tb02262.x
  5. Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem 1999;274:21491-4. https://doi.org/10.1074/jbc.274.31.21491
  6. Sapna G, Gokul S, Bagri-Manjrekar K. Matrix metalloproteinases and periodontal diseases. Oral Dis 2014;20:538-50. https://doi.org/10.1111/odi.12159
  7. Pozo P, Valenzuela MA, Melej C, Zaldivar M, Puente J, Martinez B, et al. Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients. J Periodontal Res 2005;40:199-207. https://doi.org/10.1111/j.1600-0765.2005.00786.x
  8. Kubota T, Itagaki M, Hoshino C, Nagata M, Morozumi T, Kobayashi T, et al. Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue. J Periodontol 2008;79:166-73. https://doi.org/10.1902/jop.2008.070159
  9. Tuter G, Kurtis B, Serdar M. Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1. J Periodontol 2002;73:487-93. https://doi.org/10.1902/jop.2002.73.5.487
  10. Marcaccini AM, Novaes AB Jr, Meschiari CA, Souza SL, Palioto DB, Sorgi CA, et al. Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy. Clin Chim Acta 2009;409:117-22. https://doi.org/10.1016/j.cca.2009.09.012
  11. Marcaccini AM, Meschiari CA, Zuardi LR, de Sousa TS, Taba M Jr, Teofilo JM, et al. Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. J Clin Periodontol 2010;37:180-90. https://doi.org/10.1111/j.1600-051X.2009.01512.x
  12. Kuula H, Salo T, Pirila E, Tuomainen AM, Jauhiainen M, Uitto VJ, et al. Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. Infect Immun 2009;77:850-9. https://doi.org/10.1128/IAI.00873-08
  13. Hernandez M, Gamonal J, Salo T, Tervahartiala T, Hukkanen M, Tjaderhane L, et al. Reduced expression of lipopolysaccharide-induced CXC chemokine in Porphyromonas gingivalis-induced experimental periodontitis in matrix metalloproteinase-8 null mice. J Periodontal Res 2011;46:58-66. https://doi.org/10.1111/j.1600-0765.2010.01310.x
  14. Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, Schade van Westrum S, et al. The TIMP2 membrane type 1 metalloproteinase "receptor" regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 1998;273:871-80. https://doi.org/10.1074/jbc.273.2.871
  15. Meschiari CA, Marcaccini AM, Santos Moura BC, Zuardi LR, Tanus-Santos JE, Gerlach RF. Salivary MMPs, TIMPs, and MPO levels in periodontal disease patients and controls. Clin Chim Acta 2013;421:140-6. https://doi.org/10.1016/j.cca.2013.03.008
  16. Kubota T, Matsuki Y, Nomura T, Hara K. In situ hybridization study on tissue inhibitors of metalloproteinases (TIMPs) mRNA-expressing cells in human inflamed gingival tissue. J Periodontal Res 1997;32:467-72. https://doi.org/10.1111/j.1600-0765.1997.tb00559.x
  17. Calderon-Montano JM, Burgos-Moron E, Perez-Guerrero C, Lopez-Lazaro M. A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 2011;11:298-344. https://doi.org/10.2174/138955711795305335
  18. Choi IS, Choi EY, Jin JY, Park HR, Choi JI, Kim SJ. Kaempferol inhibits P. intermedia lipopolysaccharide-induced production of nitric oxide through translational regulation in murine macrophages: critical role of heme oxygenase-1-mediated ROS reduction. J Periodontol 2013;84:545-55. https://doi.org/10.1902/jop.2012.120180
  19. Coimbra LS, Rossa C Jr, Guimaraes MR, Gerlach RF, Muscara MN, Spolidorio DM, et al. Influence of antiplatelet drugs in the pathogenesis of experimental periodontitis and periodontal repair in rats. J Periodontol 2011;82:767-77. https://doi.org/10.1902/jop.2010.100555
  20. Kim HK, Park HR, Lee JS, Chung TS, Chung HY, Chung J. Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues. Biogerontology 2007;8:399-408. https://doi.org/10.1007/s10522-007-9083-9
  21. Balli U, Keles GC, Cetinkaya BO, Mercan U, Ayas B, Erdogan D. Assessment of vascular endothelial growth factor and matrix metalloproteinase-9 in the periodontium of rats treated with atorvastatin. J Periodontol 2014;85:178-87. https://doi.org/10.1902/jop.2013.130018
  22. Donatelli RE, Lee SJ. How to report reliability in orthodontic research: Part 1. Am J Orthod Dentofacial Orthop 2013;144:156-61. https://doi.org/10.1016/j.ajodo.2013.03.014
  23. Kim HY. Statistical notes for clinical researchers: Evaluation of measurement error 1: using intraclass correlation coefficients. Restor Dent Endod 2013;38:98-102. https://doi.org/10.5395/rde.2013.38.2.98
  24. Klausen B. Microbiological and immunological aspects of experimental periodontal disease in rats: a review article. J Periodontol 1991;62:59-73. https://doi.org/10.1902/jop.1991.62.1.59
  25. Aiba T, Akeno N, Kawane T, Okamoto H, Horiuchi N. Matrix metalloproteinases-1 and -8 and TIMP-1 mRNA levels in normal and diseased human gingivae. Eur J Oral Sci 1996;104:562-9. https://doi.org/10.1111/j.1600-0722.1996.tb00142.x
  26. Kou Y, Inaba H, Kato T, Tagashira M, Honma D, Kanda T, et al. Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols. J Periodontol 2008;79:174-80. https://doi.org/10.1902/jop.2008.070364
  27. Yoon HY, Lee EG, Lee H, Cho IJ, Choi YJ, Sung MS, et al. Kaempferol inhibits IL-$1{\beta}$-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs. Int J Mol Med 2013;32:971-7. https://doi.org/10.3892/ijmm.2013.1468
  28. Sim GS, Lee BC, Cho HS, Lee JW, Kim JH, Lee DH, et al. Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast. Arch Pharm Res 2007;30:290-8. https://doi.org/10.1007/BF02977608
  29. Kowalski J, Samojedny A, Paul M, Pietsz G, Wilczok T. Effect of kaempferol on the production and gene expression of monocyte chemoattractant protein-1 in J774.2 macrophages. Pharmacol Rep 2005;57:107-12.
  30. Sin BY, Kim HP. Inhibition of collagenase by naturally-occurring flavonoids. Arch Pharm Res 2005;28:1152-5. https://doi.org/10.1007/BF02972978
  31. Kubota T, Nomura T, Takahashi T, Hara K. Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue. Arch Oral Biol 1996;41:253-62. https://doi.org/10.1016/0003-9969(95)00126-3
  32. Lin CW, Chen PN, Chen MK, Yang WE, Tang CH, Yang SF, et al. Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells. PLoS One 2013;8:e80883. https://doi.org/10.1371/journal.pone.0080883
  33. Ji L, Yin XX, Wu ZM, Wang JY, Lu Q, Gao YY. Ginkgo biloba extract prevents glucose-induced accumulation of ECM in rat mesangial cells. Phytother Res 2009;23:477-85. https://doi.org/10.1002/ptr.2652
  34. Lu Q, Yin XX, Wang JY, Gao YY, Pan YM. Effects of Ginkgo biloba on prevention of development of experimental diabetic nephropathy in rats. Acta Pharmacol Sin 2007;28:818-28. https://doi.org/10.1111/j.1745-7254.2007.00570.x
  35. Reddy MS, Jeffcoat MK. Methods of assessing periodontal regeneration. Periodontol 2000 1999;19:87-103. https://doi.org/10.1111/j.1600-0757.1999.tb00149.x
  36. Pang JL, Ricupero DA, Huang S, Fatma N, Singh DP, Romero JR, et al. Differential activity of kaempferol and quercetin in attenuating tumor necrosis factor receptor family signaling in bone cells. Biochem Pharmacol 2006;71:818-26. https://doi.org/10.1016/j.bcp.2005.12.023
  37. Trivedi R, Kumar S, Kumar A, Siddiqui JA, Swarnkar G, Gupta V, et al. Kaempferol has osteogenic effect in ovariectomized adult Sprague-Dawley rats. Mol Cell Endocrinol 2008;289:85-93. https://doi.org/10.1016/j.mce.2008.02.027
  38. Nepal M, Li L, Cho HK, Park JK, Soh Y. Kaempferol induces chondrogenesis in ATDC5 cells through activation of ERK/BMP-2 signaling pathway. Food Chem Toxicol 2013;62:238-45. https://doi.org/10.1016/j.fct.2013.08.034
  39. Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit JP, et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol 2003;65:35-42. https://doi.org/10.1016/S0006-2952(02)01445-4
  40. Yang L, Takai H, Utsunomiya T, Li X, Li Z, Wang Z, et al. Kaempferol stimulates bone sialoprotein gene transcription and new bone formation. J Cell Biochem 2010;110:1342-55. https://doi.org/10.1002/jcb.22649

Cited by

  1. Root extractive from Daphne genkwa benefits in wound healing of anal fistula through up-regulation of collagen genes in human skin fibroblasts vol.37, pp.2, 2016, https://doi.org/10.1042/bsr20170182
  2. Anti‐inflammatory, anti‐osteoclastic, and antioxidant activities of genistein protect against alveolar bone loss and periodontal tissue degradation in a mouse model of periodontitis vol.105, pp.9, 2016, https://doi.org/10.1002/jbm.a.36109
  3. The effect of colchicine on alveolar bone loss in ligature-induced periodontitis vol.33, pp.None, 2016, https://doi.org/10.1590/1807-3107bor-2019.vol33.0001
  4. Histopathological and biochemical evaluation of paeoniflorin administration in an experimental periodontitis model vol.61, pp.4, 2019, https://doi.org/10.2334/josnusd.18-0427
  5. Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase- 8 for the Identification of Potential Effective Inhibitors vol.17, pp.None, 2016, https://doi.org/10.2174/1570180817999200831094703
  6. Microenvironment‐induced TIMP2 loss by cancer‐secreted exosomal miR‐4443 promotes liver metastasis of breast cancer vol.235, pp.7, 2020, https://doi.org/10.1002/jcp.29507
  7. Immune modulatory and antioxidant effects of locally administrated vitamin C in experimental periodontitis in rats vol.78, pp.6, 2016, https://doi.org/10.1080/00016357.2020.1734656
  8. Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract vol.30, pp.10, 2016, https://doi.org/10.4014/jmb.2004.04016
  9. Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway vol.12, pp.None, 2021, https://doi.org/10.3389/fphar.2021.639628