TNF-α and RANKL facilitates the development of orthodontically-induced inflammatory root resorption

Tadashi Kojima, Masaru Yamaguchi, Tomokazu Yoshino, Mami Shimizu, Kunihiko Yamada, Takemi Goseki, Kazutaka Kasai

Department of Orthodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan.

DOI: 10.4236/ojst.2013.39A008                

Abstract

Background: The objective of this study was to determine the levels of tumor necrosis factor-alpha (TNF-α) and receptor activator of NF-kB ligand (RANKL) in the gingival crevicular fluid (GCF) in patients with severe root resorption after orthodontic treatment. Materials and Methods: Ten patients who had been receiving orthodontic treatment (5-control subjects and 5-severe root resorption subjects) participated in this study. GCF was collected from all patients. Subjects with severe root resorption (>1/3 of the original root length) were identified. Control group subjects with no loss of the root structure undergoing orthodontic treatment were also identified. The GCF was collected non-invasively from the mesial and distal sides of each of the upper central and lateral incisors using filter paper strips. The eluted GCF was used for a Western blot analysis with Antibodies against TNF-α and soluble RANKL (sRANKL). Ten male 6-week-old Wistar rats were subjected to orthodontic force of 50 g to induce a mesially tipping movement of the upper first molars for 7 days. The expression levels of TNF-α and RANKL proteins were determined in periodontal ligament (PDL) by immunohistochemical analysis. Results: The Western blot analysis showed that the TNF-α and sRANKL expressions were significantly higher in the severe root resorption group than in the control group. In the experimental tooth movement in vivo, resorption lacunae with multinucleated cells were observed in 50 g group. The immunoreactivity for TNF-α and RANKL was detected in PDL tissue subjected to the orthodontic force on day 7. Conclusion: These results suggest that TNF-α and RANKL play important roles in inducing or facilitating the development of orthodontically-induced inflammatory root resorption (OIIRR).

Keywords

TNF-α; sRANKL; Orthodontic Root Resorption; Gingival Crevicular Fluid

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Killiany, D.M. (1999) Root resorption caused by orthodontic treatment: An evidence-based review of literature. Seminars in Orthodontics, 5, 128-133. http://dx.doi.org/10.1016/S1073-8746(99)80032-2
[2]	Krishnan, V. and Davidovitch, Z. (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. American Journal of Orthodontics and Dentofacial Orthopedics, 129, 469.e1-e32.
[3]	Meikle, M.C. (2006) The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. European Journal of Orthodontics, 28, 221-240. http://dx.doi.org/10.1093/ejo/cjl001
[4]	Yamaguchi, M., Aihara, N., Kojima, T. and Kasai, K. (2006) RANKL increase in compressed periodontal ligament cells from root resorption. Journal of Dental Research, 85, 751-756. http://dx.doi.org/10.1177/154405910608500812
[5]	Nakano, Y., Yamaguchi, M., Fujita, S., Asano, M., Saito, K. and Kasai, K. (2010) Expressions of RANKL/RANK and M-CSF/c-fms in roott resorption lacunae in rat molar by heavy orthodontic force. European Journal of Orthodontics, 33, 335-343. http://dx.doi.org/10.1093/ejo/cjq068
[6]	Erciyas, K., Sezer, U., Ustün, K., Pehlivan, Y., Kisacik, B., Senyurt, S.Z., Tarakçioglu, M. and Onat, A.M. (2013) Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients. Oral Diseases, 19, 394-400. http://dx.doi.org/10.1111/odi.12017
[7]	Redlich, K., Hayer, S., Ricci, R., David, J.P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J.S., Wagner, E.F. and Schett G. (2002) Osteoclasts are essential for TNF-alpha-mediated joint destruction. Journal of Clinical Investigation, 110, 1419-1427.
[8]	Yamaguchi, M., Yoshii, M. and Kasai, K. (2006) Relationship between substance P and interleukin-1beta in gingival crevicular fluid during orthodontic tooth movement in adults. European Journal of Orthodontics, 28, 241-246. http://dx.doi.org/10.1093/ejo/cji100
[9]	Fujita, S., Yamaguchi, M., Utsunomiya, T., Yamamoto, H. and Kasai, K. (2008) Low-energy laser stimulates tooth movement velocity via expression of RANK and RANKL. Orthodontics and Craniofacial Research, 11, 143-155. http://dx.doi.org/10.1111/j.1601-6343.2008.00423.x
[10]	Bletsa, A., Berggreen, E. and Brudvik, P. (2006) Interleukin-1alpha and tumor necrosis factor-alpha expression during the early phases of orthodontic tooth movement in rats. European Journal of Oral Sciences, 114, 423-429. http://dx.doi.org/10.1111/j.1600-0722.2006.00400.x
[11]	Lamster, I.B., Hartley, L.J. and Vogel, R.I. (1985) Development of a biochemical profile for gingival crevicular fluid. Journal of Periodontology, 56, 13-21. http://dx.doi.org/10.1902/jop.1985.56.11s.13
[12]	Kavadia-Tsatala, S., Kaklamanos, E.G. and Tsalikis, L. (2002) Effects of orthodontic treatment on gingival crevicular fluid flow rate and composition: clinical implications and applications. International Journal of Adult Orthodontics and Orthognathic Surgery, 17, 191-205.
[13]	Dudic, A., Kiliaridis, S., Mombelli, A. and Giannopoulou, C. (2006) Composition changes in gingival crevicular fluid during orthodontic tooth movement: Comparisons between tension and compression sides. European Journal of Oral Sciences, 114, 416-422. http://dx.doi.org/10.1111/j.1600-0722.2006.00387.x
[14]	Uematsu, S., Mogi, M. and Deguchi, T. (1996) Interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, epidermal growth factor, and beta 2-microglobulin levels are elevated in gingival crevicular fluid during human orthodontic tooth movement. Journal of Dental Research, 75, 562-567. http://dx.doi.org/10.1177/00220345960750010801
[15]	Iwasaki, L.R., Haack, J.E., Nickel, J.C., Reinhardt, R.A. and Petro, T.M. (2001) Human interleukin-1 beta and interleukin-1 receptor antagonist secretion and velocity of tooth movement. Archives of Oral Biology, 46, 185-189. http://dx.doi.org/10.1016/S0003-9969(00)00088-1
[16]	Nishijima, Y., Yamaguchi, M., Kojima, T., Aihara, N., Nakajima, R. and Kasai, K. (2006) Levels of RANKL and OPG in gingival crevicular fluid during orthodontic tooth movement and effect of compression force on releases from periodontal ligament cells in vitro. Orthodontics and Craniofacial Research, 9, 63-70. http://dx.doi.org/10.1111/j.1601-6343.2006.00340.x
[17]	George, A. and Evans, C.A. (2009) Detection of root resorption using dentin and bone markers. Orthodontics and Craniofacial Research, 12, 229-235. http://dx.doi.org/10.1111/j.1601-6343.2009.01457.x
[18]	Yamaguchi, M. (2009) RANK/RANKL/OPG during orthodontic tooth movement. Orthodontics and Craniofacial Research, 12, 113-119. http://dx.doi.org/10.1111/j.1601-6343.2009.01444.x
[19]	Brooks, P.J., Nilforoushan, D., Manolson, M.F., Simmons, C.A. and Gong, S.G. (2009) Molecular markers of early orthodontic tooth movement. Angle Orthodontist, 79, 1108-1113. http://dx.doi.org/10.2319/121508-638R.1
[20]	Lössdofer, S., Götz, W. and Jäger, A. (2002) Immunohistochemical localization of receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth. Calcified Tissue International, 71, 45-52. http://dx.doi.org/10.1007/s00223-001-2086-7
[21]	Ren, Y., Hazemeijer, H., de Haan, B., Qu, N. and de Vos, P. (2007) Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. Journal of Periodontology, 78, 453-458. http://dx.doi.org/10.1902/jop.2007.060261
[22]	Kook, S.H., Jang, Y.S. and Lee, J.C. (2011) Human periodontal ligament fibroblasts stimulate osteoclastogenesis in response to compression force through TNFα-mediated activation of CD4+ T cells. Journal of Cellular Biochemistry, 112, 2891-2901. http://dx.doi.org/10.1002/jcb.23205
[23]	Wong, M., Ziring, D., Korin, Y., Desai, S., Kim, S., Lin, J., Gjertson, D., Braun, J., Reed, E. and Singh, R.R. (2008) TNFalpha blockade in human diseases: mechanisms and future directions. Clinical Immunology, 126, 121-136. http://dx.doi.org/10.1016/j.clim.2007.08.013
[24]	Chan, E. and Darendeliler, M.A. (2005) Physical properties of root cementum: Part 5. Volumetric analysis of root resorption craters after application of light and heavy orthodontic forces. American Journal of Orthodontics and Dentofacial Orthopedics, 127, 186-195. http://dx.doi.org/10.1016/j.ajodo.2003.11.026
[25]	Gonzales, C., Hotokezaka, H., Yoshimatsu, M., Yozgatian, J.H., Darendeliler, M.A. and Yoshida, N. (2008) Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar. Angle Orthodontist, 78, 502-509. http://dx.doi.org/10.2319/052007-240.1
[26]	Gameiro, G.H., Nouer, D.F., Borges, D.A.M.M.B., Duarte, N.P., Bovi, A. G.M., Da Silva, A.A. and Ferraz, D.A.V. M.C. (2008) Evaluation of root resorption associated with orthodontic movement in stressed rats. Minerva Stomatologica, 57, 569-575.
[27]	Kohno, T., Matsumoto, Y., Kanno, Z., Warita, H. and Soma, K. (2002) Experimental tooth movement under light orthodontic forces: Rates of tooth movement and changes of the periodontium. Journal of Orthodontics, 29, 129-135. http://dx.doi.org/10.1093/ortho/29.2.129
[28]	Zhou, J., Feng, G., Zhou, W., Ren, A., Wu, Y., Zhang, D. and Dai, H. (2011) Expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in root resorption induced by heavy force in rats. Journal of Orofacial Orthopedics, 72, 457-468. http://dx.doi.org/10.1007/s00056-011-0050-3
[29]	Garlet, T.P., Coelho, U., Silva, J.S. and Garlet, G.P. (2007) Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans. European Journal of Oral Sciences, 115, 355-362. http://dx.doi.org/10.1111/j.1600-0722.2007.00469.x
[30]	Mitsuhashi, M., Yamaguchi, M., Kojima, T., Nakajima, R. and Kasai, K. (2011) Effects of HSP70 on the compression force-induced TNF-α and RANKL expression in human periodontal ligament cells. Inflammation Research, 60, 187-194. http://dx.doi.org/10.1007/s00011-010-0253-x
[31]	Kim, S.J., Park, K.H., Park, Y.G., Lee, S.W. and Kang, Y.G. (2013) Compressive stress induced the up-regulation of M-CSF, RANKL, TNF-α expression and the downregulation of OPG expression in PDL cells via the integrin-FAK pathway. Archives of Oral Biology, 58, 707-716. http://dx.doi.org/10.1016/j.archoralbio.2012.11.003