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Gene expression profile of pulpitis

Genes & Immunity volume 17, pages 239–243 (2016)Cite this article

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Abstract

The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine–cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

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References

  1. Bender IB . Pulpal pain diagnosis—a review. J Endod 2000; 26: 175–179.

    Article  CAS  Google Scholar 

  2. Hasselgren G, Calev D . Endodontics emergency treatment sound and simplified. N Y State Dent J 1994; 60: 31–33.

    CAS  PubMed  Google Scholar 

  3. Eriksen HM . Endodontology—epidemiologic considerations. Endod Dent Traumatol 1991; 7: 189–195.

    Article  CAS  Google Scholar 

  4. Allareddy V, Rampa S, Lee MK, Allareddy V, Nalliah RP . Hospital-based emergency department visits involving dental conditions: profile and predictors of poor outcomes and resource utilization. J Am Dent Assoc 2014; 145: 331–337.

    Article  Google Scholar 

  5. States TPCot. A costly dental destination. Pew Children's Dental Campaign 2012.

  6. Smith AJ . Pulpal responses to caries and dental repair. Caries Res 2002; 36: 223–232.

    Article  CAS  Google Scholar 

  7. Keller JF, Carrouel F, Staquet MJ, Kufer TA, Baudouin C, Msika P et al. Expression of NOD2 is increased in inflamed human dental pulps and lipoteichoic acid-stimulated odontoblast-like cells. Innate Immun 2011; 17: 29–34.

    Article  CAS  Google Scholar 

  8. Staquet MJ, Carrouel F, Keller JF, Baudouin C, Msika P, Bleicher F et al. Pattern-recognition receptors in pulp defense. Adv Dent Res 2011; 23: 296–301.

    Article  Google Scholar 

  9. Karapanou V, Kempuraj D, Theoharides TC . Interleukin-8 is increased in gingival crevicular fluid from patients with acute pulpitis. J Endod 2008; 34: 148–151.

    Article  Google Scholar 

  10. Avellan NL, Sorsa T, Tervahartiala T, Forster C, Kemppainen P . Experimental tooth pain elevates substance P and matrix metalloproteinase-8 levels in human gingival crevice fluid. Acta Odontol Scand 2008; 66: 18–22.

    Article  CAS  Google Scholar 

  11. Caviedes-Bucheli J, Arenas N, Guiza O, Moncada NA, Moreno GC, Diaz E et al. Calcitonin gene-related peptide receptor expression in healthy and inflamed human pulp tissue. Int Endod J 2005; 38: 712–717.

    Article  CAS  Google Scholar 

  12. Caviedes-Bucheli J, Gutierrez-Guerra JE, Salazar F, Pichardo D, Moreno GC, Munoz HR . Substance P receptor expression in healthy and inflamed human pulp tissue. Int Endod J 2007; 40: 106–111.

    Article  CAS  Google Scholar 

  13. Caviedes-Bucheli J, Munoz HR, Azuero-Holguin MM, Ulate E . Neuropeptides in dental pulp: the silent protagonists. J Endod 2008; 34: 773–788.

    Article  Google Scholar 

  14. Esmaeili A, Akhavan A, Bouzari M, Mousavi SB, Torabinia N, Adibi S . Temporal expression pattern of sodium channel Nav 1.8 messenger RNA in pulpitis. Int Endod J 2011; 44: 499–504.

    Article  CAS  Google Scholar 

  15. Gong Q, Jiang H, Wei X, Ling J, Wang J . Expression of erythropoietin and erythropoietin receptor in human dental pulp. J Endod 2010; 36: 1972–1977.

    Article  Google Scholar 

  16. Huang FM, Tsai CH, Yang SF, Chang YC . The upregulation of oncostatin M in inflamed human dental pulps. Int Endod J 2009; 42: 627–631.

    Article  Google Scholar 

  17. Jiang HW, Ling JQ, Gong QM . The expression of stromal cell-derived factor 1 (SDF-1) in inflamed human dental pulp. J Endod 2008; 34: 1351–1354.

    Article  Google Scholar 

  18. Korkmaz Y, Lang H, Beikler T, Cho B, Behrends S, Bloch W et al. Irreversible inflammation is associated with decreased levels of the alpha1-, beta1-, and alpha2-subunits of sGC in human odontoblasts. J Dent Res 2011; 90: 517–522.

    Article  CAS  Google Scholar 

  19. Lundy FT, About I, Curtis TM, McGahon MK, Linden GJ, Irwin CR et al. PAR-2 regulates dental pulp inflammation associated with caries. J Dent Res 2010; 89: 684–688.

    Article  CAS  Google Scholar 

  20. Mutoh N, Watabe H, Chieda K, Tani-Ishii N . Expression of Toll-like receptor 2 and 4 in inflamed pulp in severe combined immunodeficiency mice. J Endod 2009; 35: 975–980.

    Article  Google Scholar 

  21. Kokkas AB, Goulas A, Varsamidis K, Mirtsou V, Tziafas D . Irreversible but not reversible pulpitis is associated with up-regulation of tumour necrosis factor-alpha gene expression in human pulp. Int Endod J 2007; 40: 198–203.

    Article  CAS  Google Scholar 

  22. Tete S, Mastrangelo F, Scioletti AP, Tranasi M, Raicu F, Paolantonio M et al. Microarray expression profiling of human dental pulp from single subject. Clin Invest Med 2008; 31: E55–E61.

    Article  CAS  Google Scholar 

  23. McLachlan JL, Smith AJ, Bujalska IJ, Cooper PR . Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries. Biochim Biophys Acta 2005; 1741: 271–281.

    Article  CAS  Google Scholar 

  24. Kaneko T, Okiji T, Kaneko R, Sunakawa M, Kaneko M, Suda H . Gene expression analysis of acutely traumatized pulps. J Endod 2010; 36: 78–82.

    Article  Google Scholar 

  25. Seltzer S, Bender IB, Ziontz M . The dynamics of pulp inflammation: correlations between diagnostic data and actual histologic findings in the pulp. Oral Surg Oral Med Oral Pathol 1963; 16: 846–871.

    Article  CAS  Google Scholar 

  26. Ricucci D, Loghin S, Siqueira JF Jr . Correlation between clinical and histologic pulp diagnoses. J Endod 2014; 40: 1932–1939.

    Article  Google Scholar 

  27. Hasler JE, Mitchell DF . Painless pulpitis. J Am Dent Assoc 1970; 81: 671–677.

    Article  CAS  Google Scholar 

  28. Hirao K, Yumoto H, Takahashi K, Mukai K, Nakanishi T, Matsuo T . Roles of TLR2, TLR4, NOD2, and NOD1 in pulp fibroblasts. J Dent Res 2009; 88: 762–767.

    Article  CAS  Google Scholar 

  29. Hyman JJ, Cohen ME . The predictive value of endodontic diagnostic tests. Oral Surg Oral Med Oral Pathol 1984; 58: 343–346.

    Article  CAS  Google Scholar 

  30. Lundy T, Stanley HR . Correlation of pulpal histopathology and clinical symptoms in human teeth subjected to experimental irritation. Oral Surg Oral Med Oral Pathol 1969; 27: 187–201.

    Article  CAS  Google Scholar 

  31. Johnson RH, Dachi SF, Haley JV . Pulpal hyperemia—a correlation of clinical and histologic data from 706 teeth. J Am Dent Assoc 1970; 81: 108–117.

    Article  CAS  Google Scholar 

  32. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545–15550.

    Article  CAS  Google Scholar 

  33. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34: 267–273.

    Article  CAS  Google Scholar 

  34. Cunha FQ, Lorenzetti BB, Poole S, Ferreira SH . Interleukin-8 as a mediator of sympathetic pain. Br J Pharmacol 1991; 104: 765–767.

    Article  CAS  Google Scholar 

  35. Leung L, Cahill CM . TNF-alpha and neuropathic pain—a review. J Neuroinflammation 2010; 7: 27.

    Article  Google Scholar 

  36. Jin EH, Zhang E, Ko Y, Sim WS, Moon DE, Yoon KJ et al. Genome-wide expression profiling of complex regional pain syndrome. PLoS One 2013; 8: e79435.

    Article  Google Scholar 

  37. Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ . Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Br J Pharmacol 1995; 115: 1265–1275.

    Article  CAS  Google Scholar 

  38. Nakanishi T, Shimizu H, Hosokawa Y, Matsuo T . An immunohistological study on cyclooxygenase-2 in human dental pulp. J Endod 2001; 27: 385–388.

    Article  CAS  Google Scholar 

  39. Bhattacharyya S, Kelley K, Melichian DS, Tamaki Z, Fang F, Su Y et al. Toll-like receptor 4 signaling augments transforming growth factor-beta responses: a novel mechanism for maintaining and amplifying fibrosis in scleroderma. Am J Pathol 2013; 182: 192–205.

    Article  CAS  Google Scholar 

  40. Villalba M, Hott M, Martin C, Aguila B, Valdivia S, Quezada C et al. Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes. Med Microbiol Immunol 2012; 201: 371–379.

    Article  CAS  Google Scholar 

  41. Shi B, Huang Q, Tak PP, Vervoordeldonk MJ, Huang CC, Dorfleutner A et al. SNAPIN: an endogenous Toll-like receptor ligand in rheumatoid arthritis. Ann Rheum Dis 2012; 71: 1411–1417.

    Article  CAS  Google Scholar 

  42. Goh FG, Piccinini AM, Krausgruber T, Udalova IA, Midwood KS . Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation. J Immunol 2010; 184: 2655–2662.

    Article  CAS  Google Scholar 

  43. Merline R, Moreth K, Beckmann J, Nastase MV, Zeng-Brouwers J, Tralhao JG et al. Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and microRNA-21. Sci Signal 2011; 4: ra75.

    Article  Google Scholar 

  44. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA 2012; 109: E2110–E2116.

    Article  CAS  Google Scholar 

  45. Dasu MR, Devaraj S, Park S, Jialal I . Increased Toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care 2010; 33: 861–868.

    Article  CAS  Google Scholar 

  46. Jialal I, Kaur H . The role of Toll-like receptors in diabetes-induced inflammation: implications for vascular complications. Curr Diab Rep 2012; epub ahead of print 8 February 2012.

  47. Devaraj S, Tobias P, Jialal I . Knockout of Toll-like receptor-4 attenuates the pro-inflammatory state of diabetes. Cytokine 2011; 55: 441–445.

    Article  CAS  Google Scholar 

  48. Van Hassel HJ . Physiology of the human dental pulp. Oral Surg Oral Med Oral Pathol 1971; 32: 126–134.

    Article  CAS  Google Scholar 

  49. Kebschull M, Demmer RT, Grun B, Guarnieri P, Pavlidis P, Papapanou PN . Gingival tissue transcriptomes identify distinct periodontitis phenotypes. J Dent Res 2014; 93: 459–468.

    Article  CAS  Google Scholar 

  50. Jensen MP, Chen C, Brugger AM . Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain 2003; 4: 407–414.

    Article  Google Scholar 

  51. Zhong S, Zhang S, Bair E, Nares S, Khan AA . Differential expression of microRNAs in normal and inflamed human pulps. J Endod 2012; 38: 746–752.

    Article  Google Scholar 

  52. Tusher VG, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98: 5116–5121.

    Article  CAS  Google Scholar 

  53. Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG . Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. Int Endod J 2002; 35: 30–36.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was financially supported by the American Association of Endodontists Foundation (AAEF) and T90DE021986.

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Authors and Affiliations

  1. Department of Endodontics, Arthur A Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, USA

    J C Galicia

  2. Department of Endodontics, Center for Pain Research and Innovation, University of North Carolina School of Dentistry, Chapel Hill, NC, USA

    J C Galicia & A A Khan

  3. DDS Program, University of North Carolina School of Dentistry, Chapel Hill, NC, USA

    B R Henson

  4. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    J S Parker

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  1. J C Galicia
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  2. B R Henson
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  4. A A Khan
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Correspondence to A A Khan.

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Galicia, J., Henson, B., Parker, J. et al. Gene expression profile of pulpitis. Genes Immun 17, 239–243 (2016). https://doi.org/10.1038/gene.2016.14

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