The korean journal of orthodontics (대한치과교정학회지)

The Korean Association Of Orthodontists (대한치과교정학회)
권호 표지

The effect of indomethacin on the matrix metalloproteinases in canine permanent tooth eruption

인도메타신의 투여가 치아 맹출 시 기질금속단백분해 효소의 분포에 미치는 영향

  • Kang, Yoon-Goo (Department of Orthodontics, School of Dentistry, Kyunghee University) ;
  • Nam, Jong-Hyun (Department of Orthodontics, School of Dentistry, Kyunghee University) ;
  • Lee, Ki-Soo (Department of Orthodontics, School of Dentistry, Kyunghee University)
  • 강윤구 (경희대학교 치의학전문대학원 교정학교실) ;
  • 남종현 (경희대학교 치의학전문대학원 교정학교실) ;
  • 이기수 (경희대학교 치의학전문대학원 교정학교실)
  • Published : 2006.04.30
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Abstract

Tooth eruption requires remodeling of surrounding tissues. This study was aimed to investigate the effect of indomethacin on the dental follicle and paradental tissues during tooth eruption by observing the distribution and expression of MMP by the immunohistochemical method. Ten mongrel dogs of ten to twelve weeks old were divided into 5 groups; four experimental groups administered indomethacin 2 mg/Kg/day and 8 mg/Kg/day orally 2 times a day for 14 days and 7 days respectively, and the control group was administered a placebo. Permanent teeth before eruption and their surrounding tissues were selected and excised. H&E staining and immunohistochemical stainings of MMP-3 and -9 were performed and examined under the light microscope. Osteoclasts, osteoblasts, periodontal ligament cells, ameloblasts and odontoblasts of the control group all expressed MMP-3 and -9. In the experimental group, osteoclasts, osteoblasts and periodontal ligament cells showed reduced expression of MMP-3 and -9. Magnitude of MMP reduction In the experimental group showed a time and dose of indomethacin administration dependent manner. These results show that indomethacin inhibited MMP-3 and -9 expression in the dental follicle and surrounding tissues and suggest that when indomethacin is administered for long periods, tooth eruption could be delayed.

이 연구는 치낭과 그 주위 조직 세포에서 matrix metalloproteinase (MMP)-3과 -9의 발현에 대한 인도메타신의 영향을 관찰하여 인도메타신이 치아의 맹출에 미치는 영향의 일단을 규명하기 위해 시행되었다. 생후 10-12주된 10마리의 개를 실험군 8마리와 대조군 2마리로 나누고 실험군은 인도메타신을 체중에 대하여 통상적 복용량인 인도메타신 2 mg/Kg/day을 7일간 및 14일간 투여한 군과 과량의 8 mg/Kg/day을 7일간 및 14일간 투여한 군으로 나누고 대조군은 빈 캅셀을 placebo로 투여한 후 희생하고 맹출 중인 영구치 치배를 적출하여 조직 처리하고 H-E 염색 및 MMP-3과 -9에 대한 면븐염색 시행 후 광학현미경으로 검경하였다. 관찰결과 대조군에서는 파골세포, 조골세포, 치주인대 세포, 법랑모세포 및 상아모세포에서 모두 MMP-3과 -9의 발현이 뚜렷하게 관찰되었다. 대조군에 비해 인도메타신 투여군에서 파골세포, 조골세포, 치주인대 세포는 MMP-3과 -9의 발현이 억제된 소견이 관찰되었으며 인도메타신의 투여기간이 길수록 투여량이 많을수록 더 뚜렷하게 관찰되었다. 법랑모세포와 상아모세포는 대조군과 실험군의 MMP-3과 -9의 발현의 차이가 관찰되지 않았다. 이상의 결과에 의하면 prostaglandin (PG) 생합성 억제제인 인도메타신은 치낭의 파골세포, 조골세포 및 치주인대 세포에서 MhfP-3과 -9의 발현을 억제하였으며 이는 인도메타신 투여로 치아 맹출이 억제될 수 있음을 시사한다.

Keywords

References

  1. Marks SC Jr. The basic and applied biology of tooth eruption. Connect Tissue Res 1995;32:149-57 https://doi.org/10.3109/03008209509013718
  2. Cahill DR, Marks SC Jr. Tooth eruption: Evidence for the central role of the dental follicle. J Oral Pathol 1980:9:189-200 https://doi.org/10.1111/j.1600-0714.1980.tb00377.x
  3. Wise GE, Lin F. The molecular biology of initiation of tooth eruption. J Dent Res 1995;74:303-6 https://doi.org/10.1177/00220345950740010301
  4. Beertsen W, Holmbeck K, Niehof A, Bianco P, Chrysovergis K, Birkedal Hansen H, et al. On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth. Eur J Oral Sci 2002;110:445-51 https://doi.org/10.1034/j.1600-0722.2002.21384.x
  5. MacNeil RL, Berry JE, Strayhorn CL, Shigeyama Y, Somerman MJ. Expression of type I and II collagen during development of the periodontal ligament in the mouse. Arch Oral Biol 1998;43:779-87 https://doi.org/10.1016/S0003-9969(98)00054-5
  6. Ngan PW, Crock B, Varghese J, Lanese R, Shanfeld J, Davidovitch Z. Immunohistochemical assessment of the effect of chemical and mechanical stimuli on cAMP and prostaglandin E levels in human gingival fibroblasts in vitro. Arch Oral Biol 1988:33:163-74 https://doi.org/10.1016/0003-9969(88)90041-6
  7. Delaisse JM, Engsig MT, Everts V, del Carmen Ovejero M, Ferreras M, Lund L, et al. Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 2000:291:223-34 https://doi.org/10.1016/S0009-8981(99)00230-2
  8. Garnero P, Borel O, Byrjalsen I, Ferreras M, Drake FH, McQueney MS, et al. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem 1998:273:32347-52 https://doi.org/10.1074/jbc.273.48.32347
  9. Kusano K, Miyaura C, Inada M, Tamura T, Ito A, Nagase H, et al. Regulation of matrix metalloproteinases (MMP-2,-3,-9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: Association of MMP induction with bone resorption. Endocrinology 1998;139:1338-45 https://doi.org/10.1210/en.139.3.1338
  10. Kubota Y, Ninomiya T, Oka S, Takenoshita Y, Shirasuna K. Interleukin-1$\alpha$-dependent regulation of matrix metalloproteinase-9 (MMP-9) secretion and activation in the epithelial cells of odontogenic jaw cysts. J Dent Res 2000:79:1423-30 https://doi.org/10.1177/00220345000790061201
  11. Heikinheimo K, Salo T. Expression of basement membrane type IV collagen and type IV collagenases (MMP-2 and MMP-9) in human fetal teeth. J Dent Res 1995:74:1226-34 https://doi.org/10.1177/00220345950740051301
  12. Sulkala M, Larmas M, Sorsa T, Salo T, Tjaderhane L. The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth. J Dent Res 2002;81:603-7 https://doi.org/10.1177/154405910208100905
  13. Yoshiba N, Yoshiba K, Stoetzel C, Perrin-Schmitt F, Cam Y, Ruch JV, et al. Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development. Dev Dyn 2003:228:105-12 https://doi.org/10.1002/dvdy.10352
  14. Caron C, Xue J. Bartlett JD. Expression and localization of membrane type 1 matrix metalloproteinase in tooth tissues. Matrix Biol 1998:17:501-11 https://doi.org/10.1016/S0945-053X(98)90098-1
  15. Sahlberg C, Reponen P, Tryggvason K, Thesleff I. Timp-1, -2 and -3 show coexpression with gelatinase A and B during mouse tooth morphogenesis. Eur J Oral Sci 1999;107:121-30 https://doi.org/10.1046/j.0909-8836.1999.eos107208.x
  16. Grier RL 4th, Wise GF. Inhibition of tooth eruption in the rat by a bisphosphonate. J Dent Res 1998:77:8-15 https://doi.org/10.1177/00220345980770011201
  17. Bartlett JD, Zhou Z, Skobe Z, Dobeck JM, Tryggvason K. Delayed tooth eruption in membrane tvpe-1 matrix metalloproteinase deficient mice. Connect Tissue Res 2003;44:300-4 https://doi.org/10.1080/713713624
  18. Kyrkanides S, O'Banion MK, Subtelny JD. Nonsteroidal anti-inflammatory drugs in orthodontic tooth movement: Metalloproteinase activity and collagen synthesis by endothelial cells. Am J Orthod Dentofacial Orthop 2000;118:203-9 https://doi.org/10.1067/mod.2000.105872
  19. Blavier L, Delaisse JM. Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones. J Cell Sci 1995;108:3649-59
  20. Engsig MT, Chen QJ, Vu TH, Pedersen AC, Therkidsen B, Lund LR, et al. Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 2000;151:879-89 https://doi.org/10.1083/jcb.151.4.879
  21. Everts V, Delaisse JM, Korper W, Niehof A, Vaes G, Beertsen W. Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases. J Cell Physiol. 1992;150:221-31 https://doi.org/10.1002/jcp.1041500202
  22. Tervahartiala T, Pirila E, Ceponis A, Maisi P, Salo T, Tuter G, et al. The in vivo expression of the collagenolytic matrix metalloproteinases (MMP-2,-8,-13, and -14) and matrilysin (MMP-7) in adult and localized juvenile periodontitis. J Dent Res 2000;79:1969-77 https://doi.org/10.1177/00220345000790120801
  23. Golub LM, Lee HM, Greenwald RA, Ryan ME, Sorsa T, Salo T, et al. A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis. Inflamm Res 1997;46:310-9 https://doi.org/10.1007/s000110050193
  24. Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998;93:411-22 https://doi.org/10.1016/S0092-8674(00)81169-1
  25. Linsuwanont B, Takagi Y, Ohya K, Shimokawa H. Expression of matrix metalloproteinase-9 mRNA and protein during deciduous tooth resorption in bovine odontoclasts. Bone 2002;31:472-8 https://doi.org/10.1016/S8756-3282(02)00856-6
  26. Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation: Evidence that MT1- MMP (MMP-14) and gelatinase A (MMP-2) are able to generate active enzyme. J Biol Chem 1996;271:17124-31 https://doi.org/10.1074/jbc.271.29.17124
  27. Unemori EN, Bair MJ, Bauer EA, Amento EP. Stromelysin expression regulates collagenase activation in human fibroblasts: Dissociable control of two metalloproteinases by interferon-$\gamma$. J Biol Chem 1991:266:23477-82
  28. Goldhaber P, Rabadjija L, Beyer WR, Kornhauser A. Bone resorption in tissue culture and its relevance to periodontal disease. J Am Dent Assoc 1973;87:1027-33 https://doi.org/10.14219/jada.archive.1973.0010
  29. Czuszak CA, Sutherland DE, Billman MA, Stein SH. Prostaglandin E2 potentiates interleukin-1 induced interleukin-f production by human gingival fibroblasts. J Clin Periodontol 1996;23:635-40 https://doi.org/10.1111/j.1600-051X.1996.tb00587.x
  30. Offenbacher S, Heasman PA, Collins JG. Modulation of host PGE2 secretion as a determinant of periodontal disease expression. J Periodontol 1993;64:432-44
  31. Takigawa M, Takashiba S, Takahashi K, Arai H, Kurihara H, Murayama Y. Prostaglandin E2 inhibits interleukin-6 release but not its transcription in human gingival fibroblasts stimulated with interleukin-1${\beta}$ or tumor necrosis factor-${\alpha}$. J Periodontol 1994;65:1122-7 https://doi.org/10.1902/jop.1994.65.12.1122
  32. Kawaguchi H, Pilbeam CC, Harrison JR, Raisz LG. The role of prostaglandins in the regulation of bone metabolism. Clin Orthop Relat Res. 1995;313:36-46
  33. Nukaga J, Kobayashi M, Shinki T, Song H, Takada T, Takiguchi T, et al. Regulatory effects of interleukin-1${\beta}$ and prostaglandin $E_2$ on expression of receptor activator of nuclear factor-${\kappa}B$ ligand in human periodontal ligament cells. J Periodontol 2004;75:249-59 https://doi.org/10.1902/jop.2004.75.2.249
  34. Choi BK, Moon SY, Cha JH, Kim KW, Yoo YJ. Prostaglandin $E_2$ is a main mediator in receptor activator of nuclear factor-${\kappa}B$ ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii. J Periodontol 2005;76:813-20 https://doi.org/10.1902/jop.2005.76.5.813
  35. Noguchi K, Shitashige M, Ishikawa I. Involvement of cyclooxygenase -2 in interleukin-1$\alpha$-induced prostaglandin production by human periodontal ligament cells. J Periodontol 1999;70:902-8 https://doi.org/10.1902/jop.1999.70.8.902
  36. Callejas NA, Casado M, Diaz-Guerra MJ, Bosca L, Martin-Sanz P. Expression of cyclooxygenase-2 promotes the release of matrix metalloproteinase- 2 and -9 in fetal rat hepatocytes. Hepatology 2001;33:860-7 https://doi.org/10.1053/jhep.2001.23002
  37. Oh JS, Sim WJ, Cha SJ, Chi KC, Park SJ, Lim HM, et al. The effect of COX -2 inhibitor on the growth and metastasis of gastric cancer xenograft. J Korean Surg Soc 2002;62:95-102
  38. Everts V, Korper W, Jansen DC, Steinfort J, Lammerse I, Heera S, et al. Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone. FASEB J 1999;13:1219-30 https://doi.org/10.1096/fasebj.13.10.1219
  39. 이지현, 신종철, 안현영, 양동은, 권인, 이귀세라 등. 배양된 인간 영양배엽세포주에서 세균내독소에 의한 MMP-2와 MMP-9의 발현에 있어서 COX-2의 역할. 대한산부회지 2002;45:1752-7
  40. Wahl LM, Olsen CE, Sandberg AL, Mergenhagen SE. Prostaglandin regulation of macrophage collagenase production. Proc Natl Acad Sci USA 1977;74:4955-8 https://doi.org/10.1073/pnas.74.11.4955
  41. Wahl LM, Lampel LL. Regulation of human peripheral blood monocyte collagenase by prostaglandins and anti-inflammatory drugs. Cell lmmunol 1987;105:411-22 https://doi.org/10.1016/0008-8749(87)90088-8
  42. DenBesten PK, Heffernan LM, Treadwell BV, Awbrey BJ, The presence and possible functions of the matrix metalloproteinase collagenase activator protein in developing enamel matrix. Biochem J 1989;264:917-20 https://doi.org/10.1042/bj2640917
  43. Ten Cate AR. Oral histology, 4th ed. Philadelphia: Mosby; 1994