J Periodontal Implant Sci.  2013 Oct;43(5):227-232. 10.5051/jpis.2013.43.5.227.

Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health

• Tabari ZA
• Azadmehr A
• Tabrizi MA
• Hamissi J
• Ghaedi FB

• KMID: 2212031
• DOI: http://doi.org/10.5051/jpis.2013.43.5.227

Abstract

PURPOSE
The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system plays a significant role in osteoclastogenesis, activation of osteoclasts, and regulation of bone resorption. This study aimed to evaluate the use of the salivary soluble RANKL (sRANKL)/OPG ratio as a diagnostic marker for periodontitis in nonsmokers.
METHODS
Twenty-five patients with chronic periodontitis and 25 individuals with a healthy periodontium were enrolled in this study. Samples containing 5 mL of unstimulated saliva were obtained from each subject. Salivary sRANKL and OPG concentrations were determined using a standard enzyme-linked immunosorbent assay. Statistical analysis was performed using SPSS ver. 18.0.
RESULTS
The levels of sRANKL and OPG were detectable in all of the samples. Positive relationships were found between the plaque index and clinical attachment level and both the salivary concentration of sRANKL and the salivary sRANKL/OPG ratio (P<0.05). The salivary concentration of sRANKL and the sRANKL/OPG ratio were significantly higher in the periodontitis group than in the healthy group (P=0.004 and P=0.001, respectively). In contrast, the OPG concentration showed no significant differences between the groups (P=0.455).
CONCLUSIONS
These findings suggest that the salivary sRANKL/OPG ratio may be helpful in the screening and diagnosis of periodontitis. However, longitudinal studies with larger populations are needed to confirm these results.

Keyword

Biological markers; Osteoprotegerin; Periodontitis; RANK ligand; Saliva

MeSH Terms

Biomarkers
Bone Resorption
Chronic Periodontitis
Enzyme-Linked Immunosorbent Assay
Humans
Mass Screening
Osteoclasts
Osteoprotegerin
Periodontal Diseases*
Periodontitis
Periodontium
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B*
Saliva
Osteoprotegerin
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B

Figure

• 

  Figure 1 A box plot showing the salivary level of soluble receptor activator of nuclear factor kappa B ligand (sRANKL). The results in this study showed that the mean value of sRANKL was significantly different between the two groups (P=0.004).

• 

  Figure 2 A box plot showing the salivary level of osteoprotegerin (OPG). The results in this study showed that no significant difference was found between the groups (P=0.455).

• 

  Figure 3 A box plot showing the salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin (sRANKL/OPG) ratio. The results of this study indicated that the salivary sRANKL/OPG ratio differed significantly between the two groups (P=0.001).

Reference

1. Genco RJ. Current view of risk factors for periodontal diseases. J Periodontol. 1996; 67:10 Suppl. 1041–1049.

2. Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol 2000. 2009; 50:52–64.

3. Sexton WM, Lin Y, Kryscio RJ, Dawson DR 3rd, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol. 2011; 38:434–441.

4. Kaufman E, Lamster IB. Analysis of saliva for periodontal diagnosis: a review. J Clin Periodontol. 2000; 27:453–465.

5. Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol. 2011; 38:Suppl 11. 85–105.

6. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999; 20:345–357.

7. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998; 95:3597–3602.

8. Quinn JM, Horwood NJ, Elliott J, Gillespie MT, Martin TJ. Fibroblastic stromal cells express receptor activator of NF-kappa B ligand and support osteoclast differentiation. J Bone Miner Res. 2000; 15:1459–1466.

9. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun. 1999; 265:144–150.

10. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93:165–176.

11. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397:315–323.

12. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003; 423:337–342.

13. Vega D, Maalouf NM, Sakhaee K. CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007; 92:4514–4521.

14. Crotti T, Smith MD, Hirsch R, Soukoulis S, Weedon H, Capone M, et al. Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis. J Periodontal Res. 2003; 38:380–387.

15. Mogi M, Otogoto J, Ota N, Togari A. Differential expression of RANKL and osteoprotegerin in gingival crevicular fluid of patients with periodontitis. J Dent Res. 2004; 83:166–169.

16. Vernal R, Chaparro A, Graumann R, Puente J, Valenzuela MA, Gamonal J. Levels of cytokine receptor activator of nuclear factor kappaB ligand in gingival crevicular fluid in untreated chronic periodontitis patients. J Periodontol. 2004; 75:1586–1591.

17. Bostanci N, Ilgenli T, Emingil G, Afacan B, Han B, Toz H, et al. Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol. 2007; 34:370–376.

18. Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol. 2008; 79:1913–1919.

19. Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: a cross-sectional study. J Am Dent Assoc. 2006; 137:322–329.

20. Costa PP, Trevisan GL, Macedo GO, Palioto DB, Souza SL, Grisi MF, et al. Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol. 2010; 81:384–391.

21. Al-Sabbagh M, Alladah A, Lin Y, Kryscio RJ, Thomas MV, Ebersole JL, et al. Bone remodeling-associated salivary biomarker MIP-1α distinguishes periodontal disease from health. J Periodontal Res. 2012; 47:389–395.

22. Tobon-Arroyave SI, Isaza-Guzman DM, Restrepo-Cadavid EM, Zapata-Molina SM, Martinez-Pabon MC. Association of salivary levels of the bone remodelling regulators sRANKL and OPG with periodontal clinical status. J Clin Periodontol. 2012; 39:1132–1140.

23. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999; 4:1–6.

24. Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condtion. Acta Odontol Scand. 1964; 22:121–135.

25. Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975; 25:229–235.

26. Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993; 694:72–77.

27. Kinney JS, Ramseier CA, Giannobile WV. Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad Sci. 2007; 1098:230–251.

28. Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res. 2005; 40:287–293.

29. Buduneli N, Biyikoglu B, Sherrabeh S, Lappin DF. Saliva concentrations of RANKL and osteoprotegerin in smoker versus non-smoker chronic periodontitis patients. J Clin Periodontol. 2008; 35:846–852.

30. Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol. 2012; 39:239–248.