Skip to main content

Inflammatory Responses in Periodontitis with or Without Rheumatoid Arthritis Alter Salivary Metallothionein and Zinc

Biological Trace Element Research (2022)Cite this article

Abstract

Periodontitis (PD) and rheumatoid arthritis (RA) are causally linked by their common inflammatory responses, yet it is largely unknown if these inflammatory responses might have an impact on salivary metallothionein (MT), zinc (Zn), and calcium (Ca) content. In this study, we analysed salivary concentrations of pro-inflammatory (IFN-γ, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines, as well as MT, Zn, and Ca in four groups of participants, namely control (without PD or RA, n = 21), PD (n = 21), RA (n = 21), or RAPD (n = 19). As expected, an increased amount of salivary pro-inflammatory cytokines were observed in the PD, RA, and RAPD groups. While Ca concentration was not significantly different between the groups, Zn concentration was lower in the PD, RA, and RAPD groups compared to the control group (p < 0.05). These groups also expressed higher MT/Zn ratios compared to the control group (p < 0.05). Unlike the control group, concentrations of inflammatory cytokines, MT, Zn, and Ca correlated with each other in the PD, RA, and RAPD groups (p < 0.05). Additionally, comorbidity of PD and RA appears to have a cumulative immuno-pathological impact that warrants further investigation. This study suggests that, in addition to inflammatory cytokines, salivary MT and Zn could reflect the severity of PD with or without RA, hence providing an important biomarker for diagnosis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

Data Availability

The datasets generated during and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

  1. Könönen E, Gursoy M, Gursoy UK (2019) Periodontitis: a multifaceted disease of tooth-supporting tissues. J Clin Med Res 8.:https://doi.org/10.3390/jcm8081135

  2. Van Dyke TE, Sheilesh D (2005) Risk factors for periodontitis. J Int Acad Periodontol 7:3–7

    PubMed  PubMed Central  Google Scholar 

  3. Huizinga TWJ, Pincus T (2010) In the clinic. Rheumatoid arthritis. Ann Intern Med 153:ITC1–1–ITC1–15; quiz ITC1–16.https://doi.org/10.7326/0003-4819-153-1-201007060-01001

  4. Pischon N, Pischon T, Kröger J et al (2008) Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol 79:979–986. https://doi.org/10.1902/jop.2008.070501

    Article  CAS  PubMed  Google Scholar 

  5. de Pablo P, Dietrich T, McAlindon TE (2008) Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol 35:70–76

    PubMed  Google Scholar 

  6. Choi IA, Kim J-H, Kim YM et al (2016) Periodontitis is associated with rheumatoid arthritis: a study with longstanding rheumatoid arthritis patients in Korea. Korean J Intern Med 31:977–986. https://doi.org/10.3904/kjim.2015.202

    Article  PubMed  PubMed Central  Google Scholar 

  7. de Smit M, Westra J, Vissink A et al (2012) Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study. Arthritis Res Ther 14:R222. https://doi.org/10.1186/ar4061

    Article  PubMed  PubMed Central  Google Scholar 

  8. de Molon RS, Rossa C Jr, Thurlings RM, et al (2019) Linkage of periodontitis and rheumatoid arthritis: current evidence and potential biological interactions. Int J Mol Sci 20. https://doi.org/10.3390/ijms20184541

  9. Eezammuddeen NN, Vaithilingam RD, Hassan NHM, Bartold PM (2020) Association between rheumatoid arthritis and periodontitis: recent progress. Curr Oral Health Rep 7:139–153. https://doi.org/10.1007/s40496-020-00264-4

    Article  Google Scholar 

  10. Roodman GD (1993) Role of cytokines in the regulation of bone resorption. Calcif Tissue Int 53(Suppl 1):S94–S98. https://doi.org/10.1007/BF01673412

    Article  CAS  PubMed  Google Scholar 

  11. Van der Meide PH, Schellekens H (1996) Cytokines and the immune response. Cytokine Yearbook, vol 1. Springer, Netherlands, Dordrecht, pp 243–249

    Chapter  Google Scholar 

  12. Rutger Persson G (2012) Rheumatoid arthritis and periodontitis - inflammatory and infectious connections. Review of the literature. J Oral Microbiol 4. https://doi.org/10.3402/jom.v4i0.11829

  13. Cetinkaya B, Guzeldemir E, Ogus E, Bulut S (2013) Proinflammatory and anti-inflammatory cytokines in gingival crevicular fluid and serum of patients with rheumatoid arthritis and patients with chronic periodontitis. J Periodontol 84:84–93. https://doi.org/10.1902/jop.2012.110467

    Article  CAS  PubMed  Google Scholar 

  14. Rahajoe PS, Smit MJ, Kertia N et al (2019) Cytokines in gingivocrevicular fluid of rheumatoid arthritis patients: A review of the literature. Oral Dis 25:1423–1434. https://doi.org/10.1111/odi.13145

    Article  PubMed  PubMed Central  Google Scholar 

  15. Astry B, Harberts E, Moudgil KD (2011) A cytokine-centric view of the pathogenesis and treatment of autoimmune arthritis. J Interferon Cytokine Res 31:927–940. https://doi.org/10.1089/jir.2011.0094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pan W, Wang Q, Chen Q (2019) The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 11:30. https://doi.org/10.1038/s41368-019-0064-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bozkurt FY, Yetkin Ay Z, Berker E et al (2006) Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis and rheumatoid arthritis: a preliminary report. Cytokine 35:180–185. https://doi.org/10.1016/j.cyto.2006.07.020

    Article  CAS  PubMed  Google Scholar 

  18. Egefjord L, Jensen JL, Bang-Berthelsen CH et al (2009) Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis? BMC Endocr Disord 9:7. https://doi.org/10.1186/1472-6823-9-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13.https://doi.org/10.12703/P6-13

  20. Kitamura H, Morikawa H, Kamon H et al (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7:971–977. https://doi.org/10.1038/ni1373

    Article  CAS  PubMed  Google Scholar 

  21. Rahman MT, De Ley M (2017) Arsenic induction of metallothionein and metallothionein induction against arsenic cytotoxicity. Rev Environ Contam Toxicol 240:151–168. https://doi.org/10.1007/398_2016_2

    Article  CAS  PubMed  Google Scholar 

  22. Aziz J, Rahman MT, Vaithilingam RD (2021) Dysregulation of metallothionein and zinc aggravates periodontal diseases. J Trace Elem Med Biol 66:126754. https://doi.org/10.1016/j.jtemb.2021.126754

    Article  CAS  PubMed  Google Scholar 

  23. Subramanian Vignesh K, Deepe GS Jr (2017) Metallothioneins: emerging modulators in immunity and infection. Int J Mol Sci 18.:https://doi.org/10.3390/ijms18102197

  24. Coyle P, Philcox JC, Carey LC, Rofe AM (2002) Metallothionein: the multipurpose protein. Cell Mol Life Sci 59:627–647. https://doi.org/10.1007/s00018-002-8454-2

    Article  CAS  PubMed  Google Scholar 

  25. Rahman MT, Haque N, Abu Kasim NH, De Ley M (2017) Origin, function, and fate of metallothionein in human blood. Rev Physiol Biochem Pharmacol 173:41–62. https://doi.org/10.1007/112_2017_1

    Article  CAS  PubMed  Google Scholar 

  26. Rahman MT, De Ley M (2001) Metallothionein isogene transcription in red blood cell precursors from human cord blood. Eur J Biochem 268:849–856. https://doi.org/10.1046/j.1432-1327.2001.01947.x

    Article  CAS  PubMed  Google Scholar 

  27. Dohi Y, Shimaoka H, Ikeuchi M et al (2005) Role of metallothionein isoforms in bone formation processes in rat marrow mesenchymal stem cells in culture. Biol Trace Elem Res 104:57–70. https://doi.org/10.1385/BTER:104:1:057

    Article  CAS  PubMed  Google Scholar 

  28. Rahman MT, Karim MM (2018) Metallothionein: a Potential link in the regulation of zinc in nutritional immunity. Biol Trace Elem Res 182:1–13. https://doi.org/10.1007/s12011-017-1061-8

    Article  CAS  PubMed  Google Scholar 

  29. Palmiter RD (1994) Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1. Proc Natl Acad Sci U S A 91:1219–1223. https://doi.org/10.1073/pnas.91.4.1219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Taru S, Jawade R, Baghele O et al (2017) Magnesium and zinc levels in individuals having generalized chronic periodontitis. J Int Clin Dent Res Organ 9:71. https://doi.org/10.4103/jicdro.jicdro_11_17

    Article  Google Scholar 

  31. Thomas B, Prasad BR, Kumari NS et al (2019) A comparative evaluation of the micronutrient profile in the serum of diabetes mellitus Type II patients and healthy individuals with periodontitis. J Indian Soc Periodontol 23:12–20. https://doi.org/10.4103/jisp.jisp_398_18

    Article  PubMed  PubMed Central  Google Scholar 

  32. Patel RM, Varma S, Suragimath G, Zope S (2016) Estimation and comparison of salivary calcium, phosphorous, alkaline phosphatase and ph levels in periodontal health and disease a cross-sectional biochemical study. J Clin Diagn Res 10:58–61. https://doi.org/10.7860/JCDR/2016/20973.8182

    Article  Google Scholar 

  33. Oelzner P, Lehmann G, Eidner T et al (2006) Hypercalcemia in rheumatoid arthritis: relationship with disease activity and bone metabolism. Rheumatol Int 26:908–915. https://doi.org/10.1007/s00296-005-0095-y

    Article  CAS  PubMed  Google Scholar 

  34. Wood RJ, Zheng JJ (1997) High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr 65:1803–1809. https://doi.org/10.1093/ajcn/65.6.1803

    Article  CAS  PubMed  Google Scholar 

  35. Yu Q, Sun X, Zhao J et al (2019) The effects of zinc deficiency on homeostasis of twelve minerals and trace elements in the serum, feces, urine and liver of rats. Nutr Metab 16:73. https://doi.org/10.1186/s12986-019-0395-y

    Article  CAS  Google Scholar 

  36. Brewer GJ, Aster JC, Knutsen CA, Kruckeberg WC (1979) Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions. Am J Hematol 7:53–60. https://doi.org/10.1002/ajh.2830070107

    Article  CAS  PubMed  Google Scholar 

  37. Roth HP, Kirchgessner M (1988) Calmodulin, zinc and calcium concentration in tissues of zinc- and calcium-deficient rats. J Trace Elem Electrolytes Health Dis 2:73–78

    CAS  PubMed  Google Scholar 

  38. Zhang L, Feng X, McDonald JM (2003) The role of calmodulin in the regulation of osteoclastogenesis. Endocrinology 144:4536–4543. https://doi.org/10.1210/en.2003-0147

    Article  CAS  PubMed  Google Scholar 

  39. Bairwa BK, Sagar M, Gupta RC, Gupta M (2019) A comparative study of salivary and serum calcium and alkaline phosphatase in patients with osteoporosis. Med Sci Monit 7:2412. https://doi.org/10.18203/2320-6012.ijrms20192539

    Article  Google Scholar 

  40. George T, Honnamurthy JB, Shivashankara AR et al (2017) Correlation of blood and salivary levels of zinc iron and copper in head and neck cancer patients an investigational study. Avicenna J Medical Biochemistry 5:35–39. https://doi.org/10.15171/ajmb.2017.06

    Article  Google Scholar 

  41. Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4:1–6. https://doi.org/10.1902/annals.1999.4.1.1

    Article  CAS  PubMed  Google Scholar 

  42. Caton JG, Armitage G, Berglundh T et al (2018) A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J Clin Periodontol 45(Suppl 20):S1–S8. https://doi.org/10.1111/jcpe.12935

    Article  PubMed  Google Scholar 

  43. Rajesh KS, Zareena HS, Arun Kumar MS (2015) Assessment of salivary calcium, phosphate, magnesium, pH, and flow rate in healthy subjects, periodontitis, and dental caries. Contemp Clin Dent 6:461–465. https://doi.org/10.4103/0976-237X.169846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Byrne ML, O’Brien-Simpson NM, Reynolds EC et al (2013) Acute phase protein and cytokine levels in serum and saliva: a comparison of detectable levels and correlations in a depressed and healthy adolescent sample. Brain Behav Immun 34:164–175. https://doi.org/10.1016/j.bbi.2013.08.010

    Article  CAS  PubMed  Google Scholar 

  45. Äyräväinen L, Heikkinen AM, Kuuliala A et al (2018) Inflammatory biomarkers in saliva and serum of patients with rheumatoid arthritis with respect to periodontal status. Ann Med 50:333–344. https://doi.org/10.1080/07853890.2018.1468922

    Article  CAS  PubMed  Google Scholar 

  46. Rajapriya P, Saravanan P, Burnice NK, et al (2014) Recent advances in salivary proteomics, genomics and transcriptomics: a reliable tool in periodontal diagnosis – a review. Ann Dent 21:8–16.  https://doi.org/10.22452/adum.vol21no2.4

  47. Mierzecki A, Strecker D, Radomska K (2011) A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 143:854–862. https://doi.org/10.1007/s12011-010-8952-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jaedicke KM, Preshaw PM (2000) Taylor JJ (2016) Salivary cytokines as biomarkers of periodontal diseases. Periodontol 70:164–183. https://doi.org/10.1111/prd.12117

    Article  Google Scholar 

  49. Myint A-M, Leonard BE, Steinbusch HWM, Kim Y-K (2005) Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord 88:167–173. https://doi.org/10.1016/j.jad.2005.07.008

    Article  CAS  PubMed  Google Scholar 

  50. Panezai J, Ghaffar A, Altamash M et al (2017) Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters. PLoS ONE 12:e0188945. https://doi.org/10.1371/journal.pone.0188945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Simon NM, McNamara K, Chow CW et al (2008) A detailed examination of cytokine abnormalities in major depressive disorder. Eur Neuropsychopharmacol 18:230–233. https://doi.org/10.1016/j.euroneuro.2007.06.004

    Article  CAS  PubMed  Google Scholar 

  52. Costa PP, Trevisan GL, Macedo GO et al (2010) Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol 81:384–391. https://doi.org/10.1902/jop.2009.090510

    Article  CAS  PubMed  Google Scholar 

  53. Teles RP, Likhari V, Socransky SS, Haffajee AD (2009) Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodontal Res 44:411–417. https://doi.org/10.1111/j.1600-0765.2008.01119.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Javed F, Ahmed HB, Mikami T et al (2014) Cytokine profile in the gingival crevicular fluid of rheumatoid arthritis patients with chronic periodontitis. J Investig Clin Dent 5:1–8. https://doi.org/10.1111/jicd.12066

    Article  PubMed  Google Scholar 

  55. Miranda TS, Heluy SL, Cruz DF et al (2019) The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and/or smoking habit. Clin Oral Investig 23:641–650. https://doi.org/10.1007/s00784-018-2471-5

    Article  PubMed  Google Scholar 

  56. Chizzolini C, Dayer J-M, Miossec P (2009) Cytokines in chronic rheumatic diseases: is everything lack of homeostatic balance? Arthritis Res Ther 11:246. https://doi.org/10.1186/ar2767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tan Y, Qi Q, Lu C et al (2017) Cytokine imbalance as a common mechanism in both psoriasis and rheumatoid arthritis. Mediators Inflamm 2017:2405291. https://doi.org/10.1155/2017/2405291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang W, Shao S, Jiao Z et al (2012) The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheumatoid arthritis. Rheumatol Int 32:887–893. https://doi.org/10.1007/s00296-010-1710-0

    Article  CAS  PubMed  Google Scholar 

  59. Acharya AB, Thakur S, Muddapur MV, Kulkarni RD (2017) Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus. Diabetes Metab Syndr 11:277–278. https://doi.org/10.1016/j.dsx.2016.12.007

    Article  PubMed  Google Scholar 

  60. Górska R, Gregorek H, Kowalski J et al (2003) Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol 30:1046–1052. https://doi.org/10.1046/j.0303-6979.2003.00425.x

    Article  PubMed  Google Scholar 

  61. Holmlund A, Hänström L, Lerner UH (2004) Bone resorbing activity and cytokine levels in gingival crevicular fluid before and after treatment of periodontal disease. J Clin Periodontol 31:475–482. https://doi.org/10.1111/j.1600-051X.2004.00504.x

    Article  CAS  PubMed  Google Scholar 

  62. Zhao B, Ivashkiv LB (2011) Negative regulation of osteoclastogenesis and bone resorption by cytokines and transcriptional repressors. Arthritis Res Ther 13:234. https://doi.org/10.1186/ar3379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Luchian I, Moscalu M, Goriuc A, et al (2021) Using salivary MMP-9 to successfully quantify periodontal inflammation during orthodontic treatment. J Clin Med Res 10.:https://doi.org/10.3390/jcm10030379

  64. Silosi I, Cojocaru M, Foia L et al (2015) Significance of circulating and crevicular matrix metalloproteinase-9 in rheumatoid arthritis-chronic periodontitis association. J Immunol Res 2015:218060. https://doi.org/10.1155/2015/218060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zalewska M, Trefon J, Milnerowicz H (2014) The role of metallothionein interactions with other proteins. Proteomics 14:1343–1356. https://doi.org/10.1002/pmic.201300496

    Article  CAS  PubMed  Google Scholar 

  66. Nosrati R, Kheirouri S, Ghodsi R, Ojaghi H (2019) The effects of zinc treatment on matrix metalloproteinases: A systematic review. J Trace Elem Med Biol 56:107–115. https://doi.org/10.1016/j.jtemb.2019.08.001

    Article  CAS  PubMed  Google Scholar 

  67. Franco C, Patricia H-R, Timo S, et al (2017) Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci 18.:https://doi.org/10.3390/ijms18020440

  68. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543. https://doi.org/10.2741/1817

    Article  CAS  PubMed  Google Scholar 

  69. Fatima T, Haji Abdul Rahim ZB, Lin CW, Qamar Z (2016) Zinc: a precious trace element for oral health care? J Pak Med Assoc 66:1019–1023

    PubMed  Google Scholar 

  70. Uwitonze AM, Ojeh N, Murererehe J, et al (2020) Zinc adequacy is essential for the maintenance of optimal oral health. Nutrients 12.:https://doi.org/10.3390/nu12040949

  71. Inonu E, Hakki SS, Kayis SA, Nielsen FH (2020) The Association Between Some Macro and Trace Elements in Saliva and Periodontal Status. Biol Trace Elem Res 197:35–42. https://doi.org/10.1007/s12011-019-01977-z

    Article  CAS  PubMed  Google Scholar 

  72. Kuraner T, Beksac MS, Kayakirilmaz K et al (1991) Serum and parotid saliva testosterone, calcium, magnesium, and zinc levels in males, with and without periodontitis. Biol Trace Elem Res 31:43–49. https://doi.org/10.1007/BF02990358

    Article  CAS  PubMed  Google Scholar 

  73. Najeeb S, Zafar MS, Khurshid Z, et al (2016) The role of nutrition in periodontal health: an update. Nutrients 8.:https://doi.org/10.3390/nu8090530

  74. Natto ZS, Abu Ahmad RH, Alsharif LT et al (2018) Chronic periodontitis case definitions and confounders in periodontal research: a systematic assessment. Biomed Res Int 2018:4578782. https://doi.org/10.1155/2018/4578782

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Philip Han, Dr. Lew Pit Hui, and Dr. Lee Yin Hui for performing the dental examinations and sample collection, and Ms. Yuen Sze Wan for her support and language editing.

Funding

This work was supported by a grant (FP017-2017A) under the Fundamental Research Grant Scheme from the Ministry of Higher Education, Malaysia.

Author information

Authors and Affiliations

  1. Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Jazli Aziz & Rathna Devi Vaithilingam

  2. Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Jazli Aziz

  3. Department of Paediatric Dentistry & Orthodontics, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Zamri Radzi

  4. Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Mohammad Tariqur Rahman

Authors
  1. Jazli Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rathna Devi Vaithilingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zamri Radzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Tariqur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jazli Aziz. The first draft of the manuscript was written by Jazli Aziz and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad Tariqur Rahman.

Ethics declarations

Ethics Approval

Ethical approval was obtained from the Medical Ethics Committee, Faculty of Dentistry—DF RD1707/0029(L) and the Medical Research Ethics Committee, University Malaya Medical Centre (MRECID NO: 2017510–5227).

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Aziz, J., Vaithilingam, R.D., Radzi, Z. et al. Inflammatory Responses in Periodontitis with or Without Rheumatoid Arthritis Alter Salivary Metallothionein and Zinc. Biol Trace Elem Res (2022). https://doi.org/10.1007/s12011-022-03416-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12011-022-03416-y

Keywords

  • Cytokines
  • Inflammation
  • Infection
  • Oral health
  • Dentistry