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Expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in root resorption induced by heavy force in rats

Die Expression von Osteoprotegerin und des Rezeptor-Aktivators des Nuklearfaktor-κ-B-Liganden bei der durch starke Krafteinwirkung induzierten Wurzelresorption bei Ratten

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A Correction to this article was published on 14 April 2022

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Abstract

Objective

The aim of this study was to investigate the expression patterns of osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) in root resorption during orthodontic tooth movement.

Material and methods

Forty 12-week-old male SD rats were used with the right maxillary side as the experimental group and the left maxillary side as the control group. After 1 N (100g) force was loaded on the right maxillary first molar, the rats were sacrificed on days 0, 1, 4, 8, and 12. Mesial root resorption of the first molar, the number of odontoclasts and osteoclasts, and OPG and RANKL mRNA expression were determined by hematoxylin-eosin and scanning electron microscopy, tartrate-resistant acid phosphate staining, and in situ hybridization, respectively.

Results

Serious root resorption was apparent on the pressure side of the mesial root of the right maxillary first molar on days 8 and 12. The number of odontoclasts in the cementum lacuna was elevated on days 8 and 12. OPG expression rose significantly on the tensile side, while RANKL expression increased on the pressure side. The mRNA level of RANKL was significantly elevated on days 4, 8, and 12. Moreover, the RANKL/OPG mRNA ratio was increased on the pressure side, but decreased on the tensile side.

Conclusion

Changes in the expression of RANKL mRNA and the RANKL/OPG mRNA ratio are accompanied by a parallel alteration in the number of odontoclasts and tooth resorption, suggesting crucial involvement of RANKL and OPG in tooth resorption.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war die Erforschung der Expressionsmuster von Osteoprotegerin (OPG) sowie des Rezeptor-Aktivators des Nuklearfaktor-κ-B-Liganden (RANKL) bei der Wurzelresorption während der kieferorthopädischen Zahnbewegung.

Material und Methodik

Verwendet wurden vierzig zwölf Wochen alte männliche SD-Ratten mit der rechten Oberkieferseite als Versuchsgruppe und mit der linken Oberkieferseite als Kontrollgruppe. Nach Belastung mit einer Kraft von 1 N (100 g) des ersten Molaren der rechten Oberkieferhälfte wurden die Ratten nach 0, 1, 4, 8 und 12 Tagen getötet. Die Resorption der mesialen Wurzel des ersten Molaren, die Anzahl der Odontoklasten und Osteoklasten sowie die Expression von OPG und RANKL-mRNA wurden jeweils mittels Hämatoxylin-Eosin-Färbung sowie per Rasterelektronenmikroskopie (REM) und mittels Tartratresistenter-saurer-Phosphatase-Färbung sowie In-situ-Hybridisierung bestimmt.

Ergebnisse

Am 8. und 12. Tag trat eine schwere Wurzelresorption an der Druckseite der mesialen Wurzel des ersten Molaren im rechten Oberkiefer auf. Die Zahl der Odontoklasten war am 8. und 12. Tag erhöht. Die OPG-Expression war an der Zugseite erheblich erhöht, während die RANKL-Expression an der Druckseite erhöht war. Der mRNA-Spiegel von RANKL war am 4., 8. und 12. Tag signifikant gestiegen. Darüber hinaus war das Verhältnis RANKL/OPG-mRNA an der Druckseite erhöht und an der Zugseite zurückgegangen.

Schlussfolgerungen

Die Änderungen in der Expression von RANKL-mRNA und dem RANKL/OPG-mRNA-Verhältnis gehen mit einer parallelen Veränderung der Zahl der Odontoklasten und der Zahnresorption einher, was auf eine entscheidende Beteiligung von RANKL und OPG an der Zahnresorption verweist.

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Change history

References

  1. Brudvik P, Rygh P (1993) Non-clast cells start orthodontic root resorption in the periphery of hyalinized zones. Eur J Orthod 15:467–480

    PubMed  Google Scholar 

  2. Brudvik P, Rygh P (1993) The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament. Eur J Orthod 15:249–263

    PubMed  Google Scholar 

  3. Casa MA, Faltin RM, Faltin K et al (2006) Root resorption on torqued human premolars shown by tartrate-resistant acid phosphatase histochemistry and transmission electron microscopy. Angle Orthod 76:1015–1021

    Article  PubMed  Google Scholar 

  4. Cillo JE Jr, Gassner R, Koepsel RR et al (2000) Growth factor and cytokine gene expression in mechanically strined human osteoblast-like cells: implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:147–154

    Article  PubMed  Google Scholar 

  5. Hammarstrom L, Lindskog S (1985) General morphologic aspects of resorption of teeth and alveolar bone. Int Endod J 18:93–108

    Article  PubMed  Google Scholar 

  6. Harokopakis-Hajishengallis E (2007) Physiologic root resorption in primary teeth: molecular and histological events. J Oral Sci 49:1–12

    Article  PubMed  Google Scholar 

  7. Hofbauer LC, Heufelder AE (1998) Osteoprotegerin and its cognate ligand: a new paradigm of osteoclastogenesis. Eur J Endocrinol 139:152–154

    Article  PubMed  Google Scholar 

  8. Horowitz MC, Xi Y, Wilson K et al (2001) Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev 12:9–18

    Article  PubMed  Google Scholar 

  9. Hughes DE, Dai AH, Tiffee JC et al (1996) Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta. Nat Med 2:1132–1136

    Article  PubMed  Google Scholar 

  10. Kanzaki H, Chiba M, Arai K et al (2006) Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement. Gene Ther 13:678–685

    Article  PubMed  Google Scholar 

  11. Kanzaki H, Chiba M, Sato A et al (2006) Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction. J Dent Res 85:457–462

    Article  PubMed  Google Scholar 

  12. Kanzaki H, Chiba M, Shimizu Y et al (2002) Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor B ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 17:210–220

    Article  PubMed  Google Scholar 

  13. Kanzaki H, Chiba M, Takahashi I et al (2004) Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement. J Dent Res 83:920–925

    Article  PubMed  Google Scholar 

  14. Kartsogiannis V, Zhou H, Horwod NJ et al (1999) Localization of RANKL (receptor activator of NFκB ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone 25:525–534

    Article  PubMed  Google Scholar 

  15. Katagiri T, Takahashi N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8:147–159

    Article  PubMed  Google Scholar 

  16. Kennedy DB, Joondeph DR, Osterberg SK et al (1983) The effect of extraction and orthodontic treatment on dentoalveolar support. Am J Orthod 84:183–190

    Article  PubMed  Google Scholar 

  17. King GJ, Fischlschweiger W (1982) The effect of force magnitude on extractable bone resorptive activity and cemental cratering in orthodontic tooth movement. J Dent Res 61:775–779

    Article  PubMed  Google Scholar 

  18. Kobayashi Y, Hashimoto F, Miyamoto H et al (2000) Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res 15:1924–1934

    Article  PubMed  Google Scholar 

  19. Kong YY, Feige U, Sarosi I et al (1999) Activated T cell regulated bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304–309

    Article  PubMed  Google Scholar 

  20. Kusumi A, Sakaki H, Kusumi T et al (2005) Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-B ligand in normal human osteoblasts via the p38 mitogenactivated protein kinase pathway by the application of cyclic tensile strain. J Bone Miner Metab 23:373–381

    Article  PubMed  Google Scholar 

  21. Lacey DL, Tan HL, Lu J et al (2000) Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 157:435–448

    Article  PubMed  Google Scholar 

  22. Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176

    Article  PubMed  Google Scholar 

  23. Low E, Zoellner H, Kharbanda OP et al (2005) Expression of mRNA for osteoprotegerin and receptor activator of nuclear factor kappa ß ligand (RANKL) during root resorption induced by the application of heavy orthodontic forces on rat molars. Am J Orthod and Dentofacial Orthop 128:497–503

    Article  Google Scholar 

  24. Nakano Y, Yamaguchi M, Fujita S et al (2011) Expressions of RANKL/RANK and M-CSF/c-fms in root resorption lacunae in rat molar by heavy orthodontic force. Eur J Orthod 33:335–345

    Article  PubMed  Google Scholar 

  25. Ogasawara T, Yoshimine Y, Kiyoshima T et al (2004) In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue. J Periodontal Res 39:42–49

    Article  PubMed  Google Scholar 

  26. Oshiro T, Shibasaki Y, Martin J et al (2001) Immunolocalization of vacuolar-type H + -ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NFkB ligand in odontoclasts during physiological root resorption of human deciduous teeth. Anat Rec 264:305–311

    Article  PubMed  Google Scholar 

  27. Oshiro T, Shiotani A, Shibasaki Y et al (2002) Osteoclast induction in periodontal tissue during experimental movement of incisors in osteoprotegerin-deficient mice. Anat Rec 266:218–225

    Article  PubMed  Google Scholar 

  28. Owman-Moll P, Kurol J (2000) Root resorption after orthodontic treatment in high and low risk patients: analysis of allergy as a possible predisposing factor. Eur J Orthod 22:657–663

    Article  PubMed  Google Scholar 

  29. Pan J, Zhang TX, Mi L et al (2010) Stepwise increasing and decreasing fluid shear stresses differentially regulate the function of osteoblasts. Cell Mol Bioeng 3:376–386

    Article  PubMed  Google Scholar 

  30. Sasaki T, Motegi N, Suzuki H et al (1988) Dentin resorption mediated by odontoclasts in physiological root resorption of human deciduous teeth. Am J Anat 183:303–315

    Article  PubMed  Google Scholar 

  31. Sasaki T, Shimizu T, Suzuki H et al (1989) Cytodifferentiation and degeneration of odontoclasts in physiologic root resorption of kitten deciduous teeth. Acta Anat (Basel) 135:330–340

    Google Scholar 

  32. Sasaki T (2003) Differentiation and functions of osteoclasts and odontoclasts in mineralized tissue resorption. Microsc Res Tech 61:483–495

    Article  PubMed  Google Scholar 

  33. Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22:549–553

    Article  PubMed  Google Scholar 

  34. Shiotani A, Shibasaki Y, Sasaki T (2001) Localization of receptor activator of NFkB ligand, RANKL, in periodontal tissues during experimental movement of rat molars. J Electron Microsc (Tokyo) 50:365–369

    Google Scholar 

  35. Simonet WS, Lacey DL, Dustan CR et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  PubMed  Google Scholar 

  36. Tang L, Lin Z, Li YM (2006) Effect of different magnitudes of mechanical strain on osteoblast in vitro. Biochem Biophys Res Commun 344:122–128

    Article  PubMed  Google Scholar 

  37. Theill LE, Boyle WJ, Penninger JM (2002) RANK-Land RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 20:795–823

    Article  PubMed  Google Scholar 

  38. Tsuji K, Uno K, Zhang GX et al (2004) Periodontal ligament cells under intermittent tensile stress regulate mRNA expression of osteoprotegerin and tissue inhibitor of matrix metalloprotease-1 and -2. J Bone Miner Metab 22:94–103

    Article  PubMed  Google Scholar 

  39. Tyrovola JB, Perrea D, Halazonetis DJ et al (2010) Relation of soluble RANKL and osteoprotegerin levels in blood and gingival crevicular fluid to the degree of root resorption after orthodontic tooth movement. J Oral Sci 52:299–311

    Article  PubMed  Google Scholar 

  40. Wise GE, Yao S, Zhang Q et al (2002) Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption. Arch Oral Biol 47:247–254

    Article  PubMed  Google Scholar 

  41. Wong LL, Zhu H, Liang T (2000) Changes of transforming growth factors beta 1 in rat periodontal tissue during orthodontic tooth movement. Chin J Dent Res 3:19–22

    Google Scholar 

  42. Yamaguchi M, Aihara N, Kojima T et al (2006) RANKL increase in compressed periodontal ligament cells from root resorption. J Dent Res 85:751–756

    Article  PubMed  Google Scholar 

  43. Yasuda H, Shima N, Nakagawa N et al (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337

    Article  PubMed  Google Scholar 

  44. Yasuda H, Shima N, Nakagawa N et al (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597–3602

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by grant from Chongqing Health Bureau (2009-2-145).

Danksagung

Die vorliegende Studie wurde durch ein Stipendium des Gesundheitsamtes von Chongqing (2009-2-145) unterstützt.

Conflict of interest

The corresponding author states that there are no conflicts of interest.

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

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Authors and Affiliations

  1. Department of Orthodontics, The Affiliated Hospital of Stomatology, Chongqing Medical University, NO.7 Shangqingsi Road, Yuzhong District, 400015, Chongqing, China

    J.P. Zhou, G. Feng, A.S. Ren, Y. Wu, D.M. Zhang &  H.W. Dai

  2. Department of Prosthodontics, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, China

    W.W, Zhou

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  1. J.P. Zhou
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Correspondence to H.W. Dai.

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Zhou, J., Feng, G., Zhou, W. et al. Expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in root resorption induced by heavy force in rats. J Orofac Orthop 72, 457–468 (2011). https://doi.org/10.1007/s00056-011-0050-3

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  • DOI: https://doi.org/10.1007/s00056-011-0050-3

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