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VOLUME 14 , ISSUE 6 ( June, 2023 ) > List of Articles

REVIEW ARTICLE

Calprotectin, S100A8, and S100A9: Potential Biomarkers of Periodontal Inflammation: A Scoping Review

Annie K George, Sankari Malaiappan, Betsy Joseph, Sukumaran Anil

Keywords : Biomarker, Calprotectin, Inflammation, Periodontal diseases

Citation Information : George AK, Malaiappan S, Joseph B, Anil S. Calprotectin, S100A8, and S100A9: Potential Biomarkers of Periodontal Inflammation: A Scoping Review. World J Dent 2023; 14 (6):559-567.

DOI: 10.5005/jp-journals-10015-2244

License: CC BY-NC 4.0

Published Online: 24-08-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Aim: This scoping review aims to explore evidence regarding the expression of calprotectin and its constituent homodimers in periodontal health and disease and to evaluate their potential role as biomarkers of periodontal diseases. Methodology: Prominent databases such as PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Central, Scopus, and Google Scholar were searched from January 1998 to May 2022 to collect evidence regarding the expression of calprotectin in periodontal health and disease and the potential use of this heterodimer and its constituent homodimers as biomarkers of periodontal diseases. Results: Cross-sectional studies have reported that calprotectin levels in gingival crevicular fluid, saliva, and serum are elevated in periodontal diseases than in health. It was found that calprotectin levels in oral fluids increased during the early stages of experimental gingivitis and may predict degrees of future periodontal breakdown. Experimental evidence also points out that calprotectin and its constituent homodimers in oral fluids may mirror the degree of periodontal inflammation and predict therapeutic response and disease susceptibility. Conclusion: Within the limitations of this scoping review, it can be concluded that calprotectin and its constituent homodimers have an altered expression pattern in periodontal diseases, and calprotectin in gingival crevicular fluid or saliva may be a promising biomarker of periodontal inflammation and granulocyte activity. Further, longitudinal studies are required to understand the precise role of constituent proteins of calprotectin—S100A8 and S100A9 during periodontal inflammation. Clinical significance: The diagnosis and management of periodontal diseases can be enhanced by identifying and validating a biomarker or panel that can detect disease susceptibility, early disease activity, and therapeutic response. This review elaborates on the potential of calprotectin and its subfractions as biomarkers of periodontal inflammation.

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  1. Papapanou PN, Susin C. Periodontitis epidemiology: is periodontitis under-recognized, over-diagnosed, or both? Periodontol 2000 2017;75(1):45–51. DOI: 10.1111/prd.12200
  2. Frencken JE, Sharma P, Stenhouse L, et al. Global epidemiology of dental caries and severe periodontitis - a comprehensive review. J Clin Periodontol 2017;44(Suppl 18):S94–S105. DOI: 10.1111/jcpe.12677
  3. Trombelli L, Farina R, Silva CO, et al. Plaque-induced gingivitis: case definition and diagnostic considerations. J Clin Periodontol 2018;45(Suppl 20):S44–S67. DOI: 10.1111/jcpe.12939
  4. Pruenster M, Vogl T, Roth J, et al. S100A8/A9: from basic science to clinical application. Pharmacol Ther 2016;167:120–131. DOI: 10.1016/j.pharmthera.2016.07.015
  5. Wang S, Song R, Wang Z, et al. S100A8/A9 in inflammation. Front Immunol 2018;9:1298. DOI: 10.3389/fimmu.2018.01298
  6. Wei L, Liu M, Xiong H. Role of calprotectin as a biomarker in periodontal disease. Mediators Inflamm 2019;2019:3515026. DOI: 10.1155/2019/3515026
  7. Vogl T, Ludwig S, Goebeler M, et al. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 2004;104(13):4260–4268. DOI: 10.1182/blood-2004-02-0446
  8. Damo SM, Kehl-Fie TE, Sugitani N, et al. Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens. Proc Natl Acad Sci U S A 2013;110(10):3841–3846. DOI: 10.1073/pnas.1220341110
  9. Jarlborg M, Courvoisier DS, Lamacchia C, et al. Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthritis. Arthritis Res Ther 2020;22(1):105. DOI: 10.1186/s13075-020-02190-3
  10. Hessian PA, Edgeworth J, Hogg N. MRP-8 and MRP-14, two abundant Ca(2+)—binding proteins of neutrophils and monocytes. J Leukoc Biol 1993;53(2):197–204. PMID: 8445331.
  11. Zwadlo G, Bruggen J, Gerhards G, et al. Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin Exp Immunol 1988;72(3):510–515.
  12. Vogl T, Eisenblatter M, Voller T, et al. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 2014;5:4593. DOI: 10.1038/ncomms5593
  13. Shabani F, Farasat A, Mahdavi M, et al. Calprotectin (S100A8/S100A9): a key protein between inflammation and cancer. Inflamm Res 2018;67(10):801–812. DOI: 10.1007/s00011-018-1173-4
  14. Nishikawa Y, Kajiura Y, Lew JH, et al. Calprotectin induces IL-6 and MCP-1 production via toll-like receptor 4 signaling in human gingival fibroblasts. J Cell Physiol 2017;232(7):1862–1871. DOI: 10.1002/jcp.25724
  15. Leukert N, Vogl T, Strupat K, et al. Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity. J Mol Biol 2006;359(4):961–972. DOI: 10.1016/j.jmb.2006.04.009
  16. Pathirana WGW, Chubb SP, Gillett MJ, et al. Faecal calprotectin. Clin Biochem Rev 2018;39(3):77–90.
  17. Petersen B, Wolf M, Austermann J, et al. The alarmin MRP8/14 as regulator of the adaptive immune response during allergic contact dermatitis. EMBO J 2013;32(1):100–111. DOI: 10.1038/emboj.2012.309
  18. Johne B, Fagerhol MK, Lyberg T, et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol Pathol 1997;50(3):113–123. DOI: 10.1136/mp.50.3.113
  19. Austermann J, Spiekermann C, Roth J. S100 proteins in rheumatic diseases. Nat Rev Rheumatol 2018;14(9):528–541. DOI: 10.1038/s41584-018-0058-9
  20. Eversole LR, Miyasaki KT, Christensen RE. The distribution of the antimicrobial protein, calprotectin, in normal oral keratinocytes. Arch Oral Biol 1992;37(11):963–968. DOI: 10.1016/0003-9969(92)90068-j
  21. Eversole LR, Miyasaki KT, Christensen RE. Keratinocyte expression of calprotectin in oral inflammatory mucosal diseases. J Oral Pathol Med 1993;22(7):303–307. DOI: 10.1111/j.1600-0714.1993.tb01077.x
  22. Kido J, Nishikawa S, Ishida H, et al. Identification of calprotectin, a calcium binding leukocyte protein, in human dental calculus matrix. J Periodontal Res 1997;32(4):355–361. DOI: 10.1111/j.1600-0765.1997.tb00545.x
  23. Miyasaki KT, Voganatsi A, Huynh T, et al. Calprotectin and lactoferrin levels in the gingival crevicular fluid of children. J Periodontol 1998;69(8):879–883. DOI: 10.1902/jop.1998.69.8.879
  24. Müller F, Frøland SS, Brandtzaeg P, et al. Oral candidiasis is associated with low levels of parotid calprotectin in individuals with infection due to human immunodeficiency virus. Clin Infect Dis 1993;16(2):301–302. DOI: 10.1093/clind/16.2.301
  25. Stríz I, Trebichavský I. Calprotectin - a pleiotropic molecule in acute and chronic inflammation. Physiol Res 2004;53(3):245–253. PMID: 15209531.
  26. Mahler M, Meroni PL, Infantino M, et al. Circulating calprotectin as a biomarker of COVID-19 severity. Expert Rev Clin Immunol 2021;17(5):431–443. DOI: 10.1080/1744666X.2021.1905526
  27. Simm M, Soderberg E, Larsson A, et al. Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study. Biomark Med 2016;10(8):811–818. DOI: 10.2217/bmm-2016-0032
  28. Kido J, Nakamura T, Kido R, et al. Calprotectin, a leukocyte protein related to inflammation, in gingival crevicular fluid. J Periodontal Res 1998;33(7):434–437. DOI: 10.1111/j.1600-0765.1998.tb02340.x
  29. Becerik S, Afacan B, Oztürk VÖ, et al. Gingival crevicular fluid calprotectin, osteocalcin and cross-linked N-terminal telopeptid levels in health and different periodontal diseases. Dis Markers 2011;31(6):343–352. DOI: 10.3233/DMA-2011-0849
  30. Kaner D, Bernimoulin JP, Kleber BM, et al. Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis. J Periodontal Res 2006;41(2):132–139. DOI: 10.1111/j.1600-0765.2005.00849.x
  31. Nakamura T, Kido J, Kido R, et al. The association of calprotectin level in gingival crevicular fluid with gingival index and the activities of collagenase and aspartate aminotransferase in adult periodontitis patients. J Periodontol 2000;71(3):361–367. DOI: 10.1902/jop.2000.71.3.361
  32. Kido J, Nakamura T, Kido R, et al. Calprotectin in gingival crevicular fluid correlates with clinical and biochemical markers of periodontal disease. J Clin Periodontol 1999;26(10):653–657. DOI: 10.1034/j.1600-051x.1999.261004.x
  33. Kajiura Y, Lew JH, Ikuta T, et al. Clinical significance of GCF sIL-6R and calprotectin to evaluate the periodontal inflammation. Ann Clin Biochem 2017;54(6):664–670. DOI: 10.1177/0004563216680232
  34. Que ML, Andersen E, Mombelli A. Myeloid-related protein (MRP)8/14(calprotectin) and its subunits MRP8 and MRP14 in plaque-induced early gingival inflammation. J Clin Periodontol 2004;31(11):978–984. DOI: 10.1111/j.1600-051X.2004.00594.x
  35. Loe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol (1930) 1965;36:177–187. DOI: 10.1902/jop.1965.36.3.177
  36. Kaner D, Bernimoulin JP, Dietrich T, et al. Calprotectin levels in gingival crevicular fluid predict disease activity in patients treated for generalized aggressive periodontitis. J Periodontal Res 2011;46(4):417–426. DOI: 10.1111/j.1600-0765.2011.01355.x
  37. Andersen E, Dessaix IM, Perneger T, et al. Myeloid-related protein (MRP8/14) expression in gingival crevice fluid in periodontal health and disease and after treatment. J Periodontal Res 2010;45(4):458–463. DOI: 10.1111/j.1600-0765.2009.01257.x
  38. Kido JI, Murakami S, Kitamura M, et al. Useful immunochromatographic assay of calprotectin in gingival crevicular fluid for diagnosis of diseased sites in patients with periodontal diseases. J Periodontol 2018;89(1):67–75. DOI: 10.1902/jop.2017.170206
  39. Kajiura Y, Bando M, Inagaki Y, et al. Glycated albumin and calprotectin levels in gingival crevicular fluid from patients with periodontitis and type 2 diabetes. J Periodontol 2014;85(12):1667–1675. DOI: 10.1902/jop.2014.140241
  40. Gao H, Xu J, He L, et al. Calprotectin levels in gingival crevicular fluid and serum of patients with chronic periodontitis and type 2 diabetes mellitus before and after initial periodontal therapy. J Periodontal Res 2021;56(1):121–130. DOI: 10.1111/jre.12800
  41. Afacan B, Çınarcık S, Gürkan A, et al. Full-mouth disinfection effects on gingival fluid calprotectin, osteocalcin, and N-telopeptide of Type I collagen in severe periodontitis. J Periodontol 2020;91(5):638–650. DOI: 10.1002/JPER.19-0445
  42. Zhou M, Meng HX, Zhao YB, et al. Changes of four proinflammatory proteins in whole saliva during experimental gingivitis. Chin J Dent Res 2012;15(2):121–127.
  43. Holmström SB, Lira-Junior R, Zwicker S, et al. MMP-12 and S100s in saliva reflect different aspects of periodontal inflammation. Cytokine 2019;113:155–161. DOI: 10.1016/j.cyto.2018.06.036
  44. Haigh BJ, Stewart KW, Whelan JR, et al. Alterations in the salivary proteome associated with periodontitis. J Clin Periodontol 2010;37(3):241–247. DOI: 10.1111/j.1600-051X.2009.01525.x
  45. Lira-Junior R, Öztürk VÖ, Emingil G, et al. Salivary and serum markers related to innate immunity in generalized aggressive periodontitis. J Periodontol 2017;88(12):1339–1347. DOI: 10.1902/jop.2017.170287
  46. Sun X, Meng H, Shi D, et al. Analysis of plasma calprotectin and polymorphisms of S100A8 in patients with aggressive periodontitis. J Periodontal Res 2011;46(3):354–360. DOI: 10.1111/j.1600-0765.2011.01350.x
  47. Haririan H, Andrukhov O, Pablik E, et al. Comparative analysis of calcium-binding myeloid-related protein-8/14 in saliva and serum of patients with periodontitis and healthy individuals. J Periodontol 2016;87(2):184–192. DOI: 10.1902/jop.2015.150254
  48. Lira-Junior R, Bissett SM, Preshaw PM, et al. Levels of myeloid-related proteins in saliva for screening and monitoring of periodontal disease. J Clin Periodontol 2021;48(11):1430–1440. DOI: 10.1111/jcpe.13534
  49. Kamatham SA, Chava VK. Comparison of salivary calprotectin levels in periodontitis associated with diabetes mellitus after low-level laser therapy as an adjunct to scaling and root planing: a randomized clinical trial. J Indian Soc Periodontol 2022;26(2):143–150. DOI: 10.4103/jisp.jisp_149_21
  50. Kojima T, Andersen E, Sanchez JC, et al. Human gingival crevicular fluid contains MRP8(S100A8) and MRP14(S100A9), two calcium-binding proteins of the S100 family. J Dent Res 2000;79(2):740–747. DOI: 10.1177/00220345000790020701
  51. Lundy FT, Chalk R, Lamey PJ, et al. Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC. J Clin Periodontol 2001;28(12):1172–1177. DOI: 10.1034/j.1600-051x.2001.281213.x
  52. Shin MS, Kim YG, Shin YJ, et al. Deep sequencing salivary proteins for periodontitis using proteomics. Clin Oral Investig 2019;23(9):3571–3580. DOI: 10.1007/s00784-018-2779-1
  53. Liu M, Won Lee J, Jung S, et al. Ability of S100 proteins and matrix metalloproteinase-9 to identify periodontitis in a ligature-induced periodontitis dog model. J Clin Periodontol 2020;47(2):182–192. DOI: 10.1111/jcpe.13215
  54. Karna S, Shin YJ, Kim S, et al. Salivary S100 proteins screen periodontitis among Korean adults. J Clin Periodontol 2019;46(2):181–188. DOI: 10.1111/jcpe.13059
  55. Kim HD, Karna S, Shin Y, et al. S100A8 and S100A9 in saliva, blood and gingival crevicular fluid for screening established periodontitis: a cross-sectional study. BMC Oral Health 2021;21(1):388. DOI: 10.1186/s12903-021-01749-z
  56. Kim HD, Kim S, Jeon S, et al. Diagnostic and prognostic ability of salivary MMP-9 and S100A8 for periodontitis. J Clin Periodontol 2020;47(10):1191–1200. DOI: 10.1111/jcpe.13349
  57. Gao H, Hou J, Meng H, et al. Proinflammatory effects and mechanisms of calprotectin on human gingival fibroblasts. J Periodontal Res 2017;52(6):975–983. DOI: 10.1111/jre.12465
  58. Gao H, Zhang X, Zheng Y, et al. S100A9-induced release of interleukin (IL)—6 and IL-8 through toll-like receptor 4(TLR4) in human periodontal ligament cells. Mol Immunol 2015;67(2 Pt B):223–232. DOI: 10.1016/j.molimm.2015.05.014
  59. Zheng Y, Hou J, Peng L, et al. The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells. PLoS One 2014;9(10):e110421. DOI: 10.1371/journal.pone.0110421
  60. Naruishi K, Nagata T. Biological effects of interleukin-6 on gingival fibroblasts: cytokine regulation in periodontitis. J Cell Physiol 2018;233(9):6393–6400. DOI: 10.1002/jcp.26521
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