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CC BY 4.0 · Eur J Dent 2022; 16(01): 173-178
DOI: 10.1055/s-0041-1731930
Original Article

Investigation of Salivary RANKL and OPG Levels in Periodontitis Patients at Hospital Universiti Sains Malaysia

Saba Asif
1   School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
,
Basaruddin Ahmad
1   School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
,
Syed Ameer Hamza
2   Department of Oral Medicine, Dental Hospital, The University of Faisalabad, Pakistan
,
Haslina Taib
1   School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
,
Nur Karyatee Kassim
1   School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
,
Siti Lailatul Akmar Zainuddin
1   School of Dental Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
› Author Affiliations Funding This study was supported by Research University Grant, Universiti Sains Malaysia (101/PPSG/8012353).
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Abstract

Objective This study was aimed to determine the levels of salivary receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and its association with periodontal status among periodontitis patients.

Materials and Methods A cross-sectional study was designed and performed at the Dental Clinic, Hospital Universiti Sains Malaysia (HUSM). Random sampling was employed to identify 88 participants into three groups: 30 mild periodontitis, 30 moderate to severe periodontitis, and 28 healthy (nonperiodontitis) patients. Periodontal parameters: periodontal pocket depth (PPD), clinical attachment level (CAL), plaque score (PS), and gingival bleeding index (GBI) were recorded. In total, 4 mL of unstimulated whole saliva was collected to determine the levels of salivary RANKL and OPG proteins by using ELISA technique. Data were analyzed by using SPSS software version 24.0.

Results Mean values for PPD (5.3 ± 0.5) and CAL (5.6 ± 0.5) were observed higher for moderate to severe periodontitis as compared with values (4.4 ± 0.2) (4.5 ± 0.2) in mild periodontitis patients. The mean salivary RANKL and OPG was 0.23 ± 0.07 ng/mL and 1.78 ± 0.70 ng/mL respectively in moderate to severe periodontitis. Only salivary RANKL levels were significantly and positively correlated with all the clinical periodontal parameters.

Conclusion The levels of salivary RANKL were higher as opposed to lower OPG levels in periodontitis patients in contrast to healthy (nonperiodontitis) patients. RANKL levels were significantly associated with the periodontal parameters. Therefore, we can conclude that RANKL can potentially aid as an adjunctive diagnostic protein in evaluating periodontal disease.

Keywords

periodontitis - receptor activator of NF-ĸB ligand - osteoprotegerin - Saliva


Publication History

Article published online:
27 September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

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  • References

  • 1 Sanz M, van Winkelhoff AJ. Working Group 1 of Seventh European Workshop on Periodontology. Periodontal infections: understanding the complexity–consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 2011; 38 (Suppl. 11) 3-6
    CrossrefPubMedGoogle Scholar
  • 2 Socransky SS. Relationship of bacteria to the etiology of periodontal disease. J Dent Res 1970; 49 (02) 203-222
    CrossrefPubMedGoogle Scholar
  • 3 Gurenlian JR. The role of dental plaque biofilm in oral health. J Dent Hyg 2007; 81: 116
    Google Scholar
  • 4 Hornef MW, Wick MJ, Rhen M, Normark S. Bacterial strategies for overcoming host innate and adaptive immune responses. Nat Immunol 2002; 3 (11) 1033-1040
    CrossrefPubMedGoogle Scholar
  • 5 Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 2003; 74 (03) 391-401
    CrossrefPubMedGoogle Scholar
  • 6 Hamza SA, Wahid A, Afzal N. et al. Effect of sodium bicarbonate mouth wash on salivary pH and interleukin-1β levels among smokers. Eur J Dent 2020; 14 (02) 260-267
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Boström L, Linder LE, Bergström J. Clinical expression of TNF-α in smoking-associated periodontal disease. J Clin Periodontol 1998; 25 (10) 767-773
    CrossrefPubMedGoogle Scholar
  • 8 Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004; 15 (01) 49-60
    CrossrefPubMedGoogle Scholar
  • 9 Takayanagi H, Iizuka H, Juji T. et al. Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 2000; 43 (02) 259-269
    CrossrefPubMedGoogle Scholar
  • 10 Yasuda H, Shima N, Nakagawa N. 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 (07) 3597-3602
    CrossrefPubMedGoogle Scholar
  • 11 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 (01) 144-150
    CrossrefPubMedGoogle Scholar
  • 12 Teng Y-TA, Nguyen H, Gao X. et al. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest 2000; 106 (06) R59-R67
    CrossrefPubMedGoogle Scholar
  • 13 Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 2003; 4 (08) 638-649
    CrossrefPubMedGoogle Scholar
  • 14 Hsu H, Lacey DL, Dunstan CR. et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A 1999; 96 (07) 3540-3545
    CrossrefPubMedGoogle Scholar
  • 15 Yasuda H, Shima N, Nakagawa N. et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998; 139 (03) 1329-1337
    CrossrefPubMedGoogle Scholar
  • 16 Kanzaki H, Chiba M, Shimizu Y, Mitani H. Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 2002; 17 (02) 210-220
    CrossrefPubMedGoogle Scholar
  • 17 Nakashima T, Kobayashi Y, Yamasaki S. et al. Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 2000; 275 (03) 768-775
    CrossrefPubMedGoogle Scholar
  • 18 Theoleyre S, Wittrant Y, Tat SK, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004; 15 (06) 457-475
    CrossrefPubMedGoogle Scholar
  • 19 Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008; 473 (02) 139-146
    CrossrefPubMedGoogle Scholar
  • 20 Kong YY, Yoshida H, Sarosi I. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999; 397 (6717) 315-323
    CrossrefPubMedGoogle Scholar
  • 21 Mizuno A, Amizuka N, Irie K. et al. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun 1998; 247 (03) 610-615
    CrossrefPubMedGoogle Scholar
  • 22 Bostanci N, Ilgenli T, Emingil G. et al. Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol 2007; 34 (05) 370-376
    CrossrefPubMedGoogle Scholar
  • 23 Vernal R, Dutzan N, Hernández M. et al. High expression levels of receptor activator of nuclear factor-kappa B ligand associated with human chronic periodontitis are mainly secreted by CD4+ T lymphocytes. J Periodontol 2006; 77 (10) 1772-1780
    CrossrefPubMedGoogle Scholar
  • 24 Lu H-K, Chen Y-L, Chang H-C, Li C-L, Kuo MY-P. Identification of the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand system in gingival crevicular fluid and tissue of patients with chronic periodontitis. J Periodontal Res 2006; 41 (04) 354-360
    CrossrefPubMedGoogle Scholar
  • 25 Behfarnia P, Saied-Moallemi Z, Javanmard SH, Naseri R. Serum, saliva, and GCF concentration of RANKL and osteoprotegerin in smokers versus nonsmokers with chronic periodontitis. Adv Biomed Res 2016; 5: 80-80
    CrossrefPubMedGoogle Scholar
  • 26 Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ. Update of the case definitions for population-based surveillance of periodontitis. J Periodontol 2012; 83 (12) 1449-1454
    CrossrefPubMedGoogle Scholar
  • 27 Jasim H, Carlsson A, Hedenberg-Magnusson B, Ghafouri B, Ernberg M. Saliva as a medium to detect and measure biomarkers related to pain. Sci Rep 2018; 8 (01) 3220
    CrossrefPubMedGoogle Scholar
  • 28 Al-Khtoum N, Qubilat AR, Al-Zaidaneen S. Al Mefleh S, Al-Qudah A. Clinical characteristics of pleomorphic adenoma of salivary glands among Jordanian patients. J Pak Med Assoc 2013; 63 (03) 358-360
    PubMedGoogle Scholar
  • 29 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
    CrossrefPubMedGoogle Scholar
  • 30 Ng PY, Donley M, Hausmann E, Hutson AD, Rossomando EF, Scannapieco FA. Candidate salivary biomarkers associated with alveolar bone loss: cross-sectional and in vitro studies. FEMS Immunol Med Microbiol 2007; 49 (02) 252-260
    CrossrefPubMedGoogle Scholar
  • 31 Sexton WM, Lin Y, Kryscio RJ. Dawson DR III, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol 2011; 38 (05) 434-441
    CrossrefPubMedGoogle Scholar
  • 32 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 (02) 166-169
    CrossrefPubMedGoogle Scholar
  • 33 Bostanci N, Saygan B, Emingil G, Atilla G, Belibasakis GN. Effect of periodontal treatment on receptor activator of NF-κB ligand and osteoprotegerin levels and relative ratio in gingival crevicular fluid. J Clin Periodontol 2011; 38 (05) 428-433
    CrossrefPubMedGoogle Scholar
  • 34 Taubman MA, Kawai T, Han X. The new concept of periodontal disease pathogenesis requires new and novel therapeutic strategies. J Clin Periodontol 2007; 34 (05) 367-369
    CrossrefPubMedGoogle Scholar
  • 35 Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol 2008; 79 (10) 1913-1919
    CrossrefPubMedGoogle Scholar
  • 36 Sakellari D, Menti S, Konstantinidis A. Free soluble receptor activator of nuclear factor-kappab ligand in gingival crevicular fluid correlates with distinct pathogens in periodontitis patients. J Clin Periodontol 2008; 35 (11) 938-943
    CrossrefPubMedGoogle Scholar
  • 37 Tang TH, Fitzsimmons TR, Bartold PM. Effect of smoking on concentrations of receptor activator of nuclear factor κB ligand and osteoprotegerin in human gingival crevicular fluid. J Clin Periodontol 2009; 36 (09) 713-718
    CrossrefPubMedGoogle Scholar
  • 38 Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol 2012; 39 (03) 239-248
    CrossrefPubMedGoogle Scholar
  • 39 Liu D, Xu JK, Figliomeni L. et al. Expression of RANKL and OPG mRNA in periodontal disease: possible involvement in bone destruction. Int J Mol Med 2003; 11 (01) 17-21
    PubMedGoogle Scholar
  • 40 Cao JJ, Wronski TJ, Iwaniec U. et al. Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse. J Bone Miner Res 2005; 20 (09) 1659-1668
    CrossrefPubMedGoogle Scholar
  • 41 Makhluf HA, Mueller SM, Mizuno S, Glowacki J. Age-related decline in osteoprotegerin expression by human bone marrow cells cultured in three-dimensional collagen sponges. Biochem Biophys Res Commun 2000; 268 (03) 669-672
    CrossrefPubMedGoogle Scholar