Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
권호 표지

Expression of Osteoprotegerin and Osteoclast Differentiation Factor in Human Periodontal Ligament Fibroblast Cells

치주인대 섬유아세포에서 Osteoprotegerin과 Osteoclast Differentiation Factor의 발현

  • Rew, Seong-Hun (Department of periodontology and Research Institute of Oral Bio-science college of Dentistry, Chonbuk National University) ;
  • Heo, Soo-Rew (Department of periodontology and Research Institute of Oral Bio-science college of Dentistry, Chonbuk National University) ;
  • Kim, Hyung-Seop (Department of periodontology and Research Institute of Oral Bio-science college of Dentistry, Chonbuk National University) ;
  • O, Kwi-Ok (Oscotec Inc)
  • 류성훈 (전북대학교 치과대학 치주과학교실, 전북대학교 구강생체과학연구소) ;
  • 허수례 (전북대학교 치과대학 치주과학교실, 전북대학교 구강생체과학연구소) ;
  • 김형섭 (전북대학교 치과대학 치주과학교실, 전북대학교 구강생체과학연구소) ;
  • 오귀옥 ((주) Oscotec)
  • Published : 2002.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Recently, soluble TNF receptor homolog osteoprotegerin(OPG) and its membrane-bound ligand osteoclast differentiation factor(ODF) were found to regulate osteoclast formation and function, and bone metabolism. It is now well established that ODF acts via RANK expressed on hematopoietic osteoclast precursor cells to facilitate their differentiation to osteoclasts, and OPG prevents the formation of osteoclasts by interfering the binding of ODF and RANK. Expression of OPG and ODF was believed to be closely related to the pathogenesis of bone resorption and destruction from osteoporosis, periodontal diseases, malignant bone tumor, and arthritis. The periodontal ligament fibroblasts (PDLF), located between the tooth and tooth socket, has been thought to play an important role in maintaining bone homeostasis of periodontal tissues. However, the exact mechanism by which bone formation and resorption are regulated by PDLF is not well understood. In this study we have prepared primary cultures of human PDLF from periodontium of malaligned tooth extracted due to orthodontic reason, and determined steady state or inflammatory signal-induced OPG and ODF expression using RT-PCR and western blot analysis. OPG and ODF mRNA and protein were expressed constitutively in the PDLF and these expression were slightly increased by osteotropic cytokine IL-1 ${\beta}$. Lipopolysaccharide-treated PDLF showed decrease in OPG mRNA and protein expression, and increase in ODF mRNA and protein expression. These results indicated that PDLF influence the osteoclastogenesis by OPG and ODF expression in the inflammatory situation as well as physiological condition, and thereby pathogenesis of periodontal alveolar bone destruction.

Keywords

References

  1. Chambers TJ, Hall TJ : Cellular and molecular mechanism in the regulation and function of osteoclast. vitam horm,1991;46:41-86 https://doi.org/10.1016/S0083-6729(08)60682-2
  2. Kolliker A : Die normale resorption des knochengewebes und irhe bedentung fur die eststehung der typischen knochenformen. F.C.W.Vogel,Leipzig1873
  3. Suda T, Takahashi N, Martin TJ : Modulation of osteoclast differentiation. Endocrinol rev, 1992;13:66-88
  4. Suda T, Udagawa N, Takahashi N : Cell of bone: osteoclast generation, principles of bone biology chapter. 1996;7:87-99
  5. Quinn J, Elliott J, Gillespie M, Martin T : A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro. Endocrinology, 1998;139
  6. Takahashi N, Udagawa N, Suda T: A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteo-clast differentiation and function. Biochem. Biophys, Res. Commun, 1999;256:449-455 https://doi.org/10.1006/bbrc.1999.0252
  7. Tsuda E, Goto M, Mochizuki S : Isolation of a novel cytokine from fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997;234:137-142 https://doi.org/10.1006/bbrc.1997.6603
  8. Yasuda H, Shima N, Nakagawa N : Identity of Osteoclastogenesis inhibitory factor (OCIF) and Osteoprotegerin(OPG) : a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology,1998;139:1329-1337 https://doi.org/10.1210/en.139.3.1329
  9. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin / losteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Cell Biol,1998;95:3597-3602
  10. Hakeda Y, Kobayashi Y,Yamaguchi M et al. Osteoclastogenesis inhibitory factor(OCIF) directly inhibits bone resorbing activity of isolated mature osteoclast. Biochem Biophys Res Commun,1998;251:796-801 https://doi.org/10.1006/bbrc.1998.9523
  11. Kwon B.S, Wang S, Udagawa N, Haridas V, Lee Z.H, Kim K.K, Oh K.O, Greene J, Li Y, Su J, Gentz R, Aggarwal B.B, Ni J, TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption. FASEB J,1998;12:845-854
  12. Lacey DL, Timms E, Tan HL. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell,1998;93:165-176 https://doi.org/10.1016/S0092-8674(00)81569-X
  13. Horwood NJ, Kartsogiannis V, Quinn JMW, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun, 1999;265:144-150 https://doi.org/10.1006/bbrc.1999.1623
  14. Wong BR, Rho J, Arron J, TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Bioi Chem,1997;272: 25190-25194 https://doi.org/10.1074/jbc.272.40.25190
  15. Anderson DM, Marakoskovsky E, Billingsley WL. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic cell function. Nature,1997;390:175-179 https://doi.org/10.1038/36593
  16. Matsuzaki K, Udagawa N, Takahashi N. Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures. Biochem Biophys Res Commun,1998;246:199-204 https://doi.org/10.1006/bbrc.1998.8586
  17. Burgess TL, Qian YX, Kaufman S. The ligand for osteoprotegerin(OPGL) directly activates mature osteoclasts. J Cell Biol,1999;145:527-538 https://doi.org/10.1083/jcb.145.3.527
  18. Jimi E, Akiyama S, Tsurukai T, Okahashi N, Kobayashi K, Udagawa N, Nishihara T, Takahashi N, Suda T. Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J Immunol,1999;163:434-442
  19. Kong YY, Yoshida H, Saroshi I. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis. Nature,1997;397:315-323 https://doi.org/10.1038/16852
  20. Kartsogiannis Y, Zhou H, Horwood NJ. Localization of RANKL(Receptor activator of NF-kB ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone,1999;25:525-534 https://doi.org/10.1016/S8756-3282(99)00214-8
  21. Freeman E, Periodontium. In: Ten Cate AR, ed. Oral histology: development,structure.and function. St Louis:Mosby,1994:276-312
  22. Groeneveld MC, Everts V, Beertsen W. Alkaline phosphatase activity in the periodontal ligament and gingiva of the rat molar: its relation to cementum formation. J Dent Res,1995;74:1374-1381 https://doi.org/10.1177/00220345950740070901
  23. Beertsen W, van den Bos T. Alkaline phosphatase induces the mineralization of sheets of collagen implanted subcutaneously in the rat, J Clin Invest,1992;89:1974-1980 https://doi.org/10.1172/JCI115805
  24. Groeneveld MC, Everts V, Beertsen W. Formation of afibrillar acellular cementum-like layers induced by alkaline phosphatase activity from periodontal ligament explants maintained in vitro. J Dent Res,1994;73:1588-1592 https://doi.org/10.1177/00220345940730100201
  25. Giniger MS, Norton L, Sousa S, Lorenzo JA, Bronner F. A human periodontal ligament fibroblast clone releases a bone resorption inhibition factor in vitro. J Dent Res,1991;70:99-101 https://doi.org/10.1177/00220345910700021901
  26. Rowe DJ, Leung WW, Del Cario DL. Osteoclast inhibition by factors from cells associated with regenerative tissue. J Periodontol,1996;67:414-421 https://doi.org/10.1902/jop.1996.67.4.414
  27. Sakata M, Shiba H, Komatsuzawa H et al, Expression of osteoprotegerin(osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells. J Bone Miner Res,1999;14:1486-1492 https://doi.org/10.1359/jbmr.1999.14.9.1486
  28. Wada N, Maeda H, Tanabe K, Tsuda E, Yano K, Nakamuta H, Akamine A. Periodontal ligament cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin/osteoclastogenesis inhibitory factor. J Periodont Res,2001;36:56-63 https://doi.org/10.1034/j.1600-0765.2001.00604.x
  29. Kanzaki H, Chiba M, Shimizu, Mitani H. Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition. J Dent Res,2001;80(3):887-891 https://doi.org/10.1177/00220345010800030801
  30. Holbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenic protein-2, and cytokines, Biochem Biophys Res Commun,1998;250:776-781 https://doi.org/10.1006/bbrc.1998.9394
  31. Holbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Interleukin 1-$\beta$ and tumor necrosis factor-$\alpha$, but not interleukin-6 stimulate osteoprotegerin ligand mRNA levels in human osteoblastic cells. Bone,1999;24(in press)
  32. Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N. Modulation of osteoclast differentiation by local factors. Bone,1995;17(suppl):87s-91s https://doi.org/10.1016/8756-3282(95)00185-G
  33. Felix R, Fleisch H, Elford PR. Bone-resorbing cytokines enhance release of macrophage colony-stimulating activity by the osteoblastic cell MC3T3-E1. Calcif Tissue Int,1989;44:356-360 https://doi.org/10.1007/BF02556317
  34. Page RC. The role of inflammatory mediators in the pathogenesis of periodontal disease. J Periodont Res,1991;26:230-242 https://doi.org/10.1111/j.1600-0765.1991.tb01649.x
  35. Yamaji Y, Kubota T, Sasaguri K, Sato S, Suzuki Y, Kumada H, Umemoto T. Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. Infect Immun,1995;63:3576-3581
  36. Morrison DC, Cuncan Jr, J.L, and Goodman SA. In vitro biological activities of endotoxin. In Bacterial Endotoxin,1985;81-98
  37. Hausmann E, Weingeld N, Miller W.A. Effect of lipopolysaccharide on bone resorption in tissue culture. Calcif Tissue Res,1972;9:272 https://doi.org/10.1007/BF02061967
  38. Raisz LG, Nuki K, Alander CB, Craig RG. Interactions between bacterial endotoxin and other stimulators of bone resorption in organ culture. J Periodon Res,1981;16:1 https://doi.org/10.1111/j.1600-0765.1981.tb00943.x
  39. Chaudhary LR, Spelsberg TC, Riggs BL. Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 and tumor necrosis factor- ; lack of regulatory by 17-estradiol. Endocrinology,1992;130:2528-2534 https://doi.org/10.1210/en.130.5.2528
  40. 김태선, 유윤정, 곽월이, 이승일, 이종갑. Interleukin-1$\beta$에 의하여 치주인대세포에서 유리된 cytokine이 파골세포 형성에 미치는 영향. 대한소아치과학회지,1996;23:189-204
  41. Sakata M, Shiba H, Komatsuzawa H et al. Expression of osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells. J Bone Miner Res,1999;14:1486-1492 https://doi.org/10.1359/jbmr.1999.14.9.1486
  42. Beresford JN, Gallagher JA, Russell RG. 1,25-Dihydroxyvitamin D3 and human bone derived cells in vitro; Effects on alkaline phosphatase, type I collagen and proliferation. Endocrinology, 1986;199:1776-1785
  43. Endo H, Kitoki M, Kawashima K, Naruchi T, Hashimoto Y. Vitamin D metabolites and PTH synergistically stimulate bone formation of chick embryonic femur in vitro. Nature,1980;286:262-264 https://doi.org/10.1038/286262a0
  44. Chen TL, Cone Cm, Feldman D. Effects of 1,25-dihydroxyvitamin D3 and glucocorticoids on the growth of rat and mouse osteoblast-like cells. Calcif Tissue Int,1983;35:806-811 https://doi.org/10.1007/BF02405127
  45. 김성우, 박동권, 김상철. 1,25-Dihydroxyvitarnin $D_{3S}$가 치주인대세포활성 및 실험적 치아이동에 미치는 영향에 관한연구. 대한치과교정학회지,1997;27(2):335-347
  46. Holbauer LC, Gori F, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells; potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology,1999(in press)