Pulpa ve Periapikal Doku Hastalıklarının Biyokimyası

oral-biyokimya

Deniz Yanık, Fügen Dağlı Cömert

Bu bölüm, pulpa ve periapikal doku hastalıklarının oluşumuna ve bu hastalık tablolarındaki çeşitli moleküler, genetik değişikliklere ve aktif sinyal yolaklarına odaklanmaktadır. Ayrıca, yüksek rejenerasyon kapasitesine sahip pulpa dokusunun sağlıktaki durumunu da biyokimyasal açıdan ortaya koymaktadır. Pulpal hastalıkların çoğu diş hekimliğinin acil tedavi gerektiren, bu yüzden hızlı ve doğru teşhis ve tedavi planı ihtiyacının en yüksek olduğu patoloji gruplarından birini oluşturur. Ne yazık ki pulpa hastalıkların klinik teşhis yöntemleri ile tanısı, pulpadaki enfeksiyonun derecesi ve dokudaki yaygınlığı hakkında bilgi sağlama konusunda yetersiz kalabilmektedir. Bu nedenle, pulpal hastalıklardaki moleküler ve genetik haritaların oluşturulması, endodonti bilimi için yeni teşhis yöntemlerinin kapısını aralayabilir. Daha ileri teşhis yöntemlerinin gelişmesi ise, gereksiz tedavilerin uygulanmasını engelleyerek dişin canlılığının daha uzun süre korunabilmesini sağlayabilir. Pulpa ve Periapikal Doku Hastalıklarının Biyokimyası bölümü, pulpa hastalıkları ve sağlığındaki biyokimyasal durumu ve değişiklikleri ortaya koymakta ve bu moleküler değişikliklerin önemine defaatle vurgu yapmaktadır.

Referanslar

  1. Abd-Elmeguid, A., Abdeldayem, M., Kline, L. W., Moqbel, R., Vliagoftis, H., & Donald, C. Y. (2013). Osteo-calcin expression in pulp inflammation. Journal of Endodontics, 39(7), 865-872.
  2. Accorsi-Mendonça, T., Silva, E. J. N. L., Marcaccini, A. M., Gerlach, R. F., Duarte, K. M. R., Pardo, A. P. S., ... & Zaia, A. A. (2013). Evaluation of gelatinases, tissue inhibitor of matrix metalloproteinase-2, and myelo-peroxidase protein in healthy and inflamed human dental pulp tissue. Journal of Endodontics, 39(7), 879-882.
  3. Adachi, T., Nakanishi, T., Yumoto, H., Hirao, K., Takahashi, K., Mukai, K., ... & Matsuo, T. (2007). Caries-re-lated bacteria and cytokines induce CXCL10 in dental pulp. Journal of Dental Research, 86(12), 1217-1222.
  4. Alghaithy, R. A., & Qualtrough, A. J. E. (2017). Pulp sensibility and vitality tests for diagnosing pulpal health in permanent teeth: a critical review. International endodontic journal, 50(2), 135-142.
  5. Al Natour, B., Lundy, F. T., About, I., Jeanneau, C., Dombrowski, Y., & El Karim, I. A. (2023). Regulation of caries-induced pulp inflammation by NLRP3 inflammasome: A laboratory-based investigation. International Endodontic Journal, 56(2), 193-202.
  6. Alptekin, N. O., Ari, H., Ataoglu, T., Haliloglu, S., Alptekin, T., & Serpek, B. (2005). Neutrophil elastase levels in periapical exudates of symptomatic and asymptomatic teeth. Journal of Endodontics, 31(5), 350-353.
  7. Alptekin, N. O., Ari, H., Haliloglu, S., Alptekin, T., Serpek, B., & Ataoglu, T. (2005). The effect of endodontic therapy on periapical exudate neutrophil elastase and prostaglandin-E2 levels. Journal of Endodontics, 31(11), 791-795.
  8. Álvarez-Vásquez, J. L., & Castañeda-Alvarado, C. P. (2022). Dental pulp fibroblast: a star cell. Journal of Endodontics, 48(8), 1005-1019.
  9. Aranha, A. M. F., Repeke, C. E., Garlet, T. P., Vieira, A. E., Campanelli, A. P., Trombone, A. P. F., ... & Garlet, G. P. (2013). Evidence supporting a protective role for th9 and th22 cytokines in human and experimental peri-apical lesions. Journal of Endodontics, 39(1), 83-87.
  10. Araujo-Pires, A. C., Francisconi, C. F., Biguetti, C. C., Cavalla, F., Aranha, A. M. F., Letra, A., ... & Garlet, G. P. (2014). Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. Journal of Applied Oral Science, 22, 336-346.
  11. Araujo-Pires, A. C., Francisconi, C. F., Biguetti, C. C., Cavalla, F., Aranha, A. M. F., Letra, A., ... & Garlet, G. P. (2014). Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. Journal of Applied Oral Science, 22, 336-346..
  12. Artese, L., Rubini, C., Ferrero, G., Fioroni, M., Santinelli, A., & Piattelli, A. (2002). Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps. Journal of Endodontics, 28(1), 20-23. Awawdeh, L., Lundy, F. T., Shaw, C., Lamey, P. J., Linden, G. J., & Kennedy, J. G. (2002). Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. International Endodontic Journal, 35(1), 30-36.
  13. Azuero-Holguin, M. M., Leal-Fernandez, M. C., Restrepo-Mejia, L. M., Velandia-Daza, G., Guzman-Quim-bayo, F., & Urquiza-Martinez, M. (2003). Identification and quantification of vasoactive intestinal peptide in periradicular lesions. Journal of Endodontics, 29(9), 557-558.
  14. Bakhsh, A., Moyes, D., Proctor, G., Mannocci, F., & Niazi, S. A. (2022). The impact of apical periodontitis, non-surgical root canal retreatment and periapical surgery on serum inflammatory biomarkers. International Endodontic Journal, 55(9), 923-937.
  15. Barkhordar, R. A., Hayashi, C., & Hussain, M. Z. (1999). Detection of interleukin-6 in human dental pulp and periapical lesions. Dental Traumatology, 15(1), 26-27.
  16. Belmar, M. J., Pabst, C., Martínez, B., & Hernández, M. (2008). Gelatinolytic activity in gingival crevicular fluid from teeth with periapical lesions. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 105(6), 801-806.
  17. Berman, L. H., & Hargreaves, K. M. (2020). Cohen’s pathways of the pulp-e-book. Elsevier Health Sciences. Bianchi, M. E. (2007). DAMPs, PAMPs and alarmins: all we need to know about danger. Journal of Leucocyte Biology, 81(1), 1-5.
  18. Biomarkers Definition Working Group. (2001). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical Pharmacology & Therapeutics, 69(3), 89-95.
  19. Bracks, I. V., Armada, L., Gonçalves, L. S., & Pires, F. R. (2014). Distribution of mast cells and macrophages and expression of interleukin-6 in periapical cysts. Journal of Endodontics, 40(1), 63-68
  20. Braz-Silva, P. H., Bergamini, M. L., Mardegan, A. P., De Rosa, C. S., Hasseus, B., & Jonasson, P. (2019). Inf-lammatory profile of chronic apical periodontitis: a literature review. Acta Odontologica Scandinavica, 77(3), 173-180.
  21. Brizuela, C., Meza, G., Mercadé, M., Inostroza, C., Chaparro, A., Bravo, I., ... & Ramírez, V. (2020). Inflamma-tory biomarkers in dentinal fluid as an approach to molecular diagnostics in pulpitis. International Endodontic Journal, 53(9), 1181-1191.
  22. Byers, M. R., Taylor, P. E., Khayat, B. G., & Kimberly, C. L. (1990). Effects of injury and inflammation on pulpal and periapical nerves. Journal of Endodontics, 16(2), 78-84.
  23. Cavalla, F., Reyes, M., Vernal, R., Álvarez, C., Paredes, R., García-Sesnich, J., ... & Hernández, M. (2013). High Levels of CXC Ligand 12/Stromal Cell–derived Factor 1 in Apical Lesions of Endodontic Origin Associ-ated with Mast Cell Infiltration. Journal of Endodontics, 39(10), 1234-1239.
  24. Caviedes-Bucheli, J., Camargo-Beltrán, C., Gómez-la-Rotta, A. M., Moreno, S. C. T., Abello, G. C. M., & González-Escobar, J. M. (2004). Expression of calcitonin gene-related peptide (CGRP) in irreversible acute pulpitis. Journal of Endodontics, 30(4), 201-204.
  25. Caviedes-Bucheli, J., Lombana, N., Azuero-Holguín, M. M., & Munoz, H. R. (2006). Quantification of neuro-peptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal polypeptide) expressed in healthy and inflamed human dental pulp. International Endodontic Journal, 39(5), 394-400.
  26. Caviedes-Bucheli, J., Muñoz, H. R., Azuero-Holguín, M. M., & Ulate, E. (2008). Neuropeptides in dental pulp: the silent protagonists. Journal of Endodontics, 34(7), 773-788.
  27. Caviedes-Bucheli, J., Muñoz, H. R., Azuero-Holguín, M. M., & Ulate, E. (2008). Neuropeptides in dental pulp: the silent protagonists. Journal of Endodontics, 34(7), 773-788.
  28. Cinelli, J., Nguyen, E., & Kingsley, K. (2019). Assessment of dental pulp stem cell (DPSC) biomarkers fol-lowing induction with bone morphogenic protein 2 (BMP-2). Advances and Trends in Biotechnology and Ge-netics, 3, 119-131.
  29. Cintra, L. T. A., Samuel, R. O., Azuma, M. M., de Queiróz, A. O. S., Ervolino, E., Sumida, D. H., ... & Go-mes-Filho, J. E. (2016). Multiple apical periodontitis influences serum levels of cytokines and nitric oxide. Journal of Endodontics, 42(5), 747-751.
  30. Coğulu, D., Oncag, O., Kutukculer, N., Uzel, A., & Eronat, C. (2007). The correlation between serum im-munoglobulin A and immunoglobulin G levels and the presence of Treponema denticola in human periapical lesions. Journal of Endodontics, 33(12), 1413-1416.
  31. Cohen, J. S., Reader, A., Fertel, R., Beck, F. M., & Meyers, W. J. (1985). A radioimmunoassay determination of the concentrations of prostaglandins E2 and F2α in painful and asymptomatic human dental pulps. Journal of endodontics, 11(8), 330-335.
  32. 􀀁olić, M., Gazivoda, D., Vu􀀂ević, D., Vasilijić, S., Rudolf, R., & Lukić, A. (2009). Proinflammatory and immu-noregulatory mechanisms in periapical lesions. Molecular immunology, 47(1), 101-113.
  33. Cotti, E., Dessì, C., Piras, A., Flore, G., Deidda, M., Madeddu, C., ... & Mercuro, G. (2011). Association of endodontic infection with detection of an initial lesion to the cardiovascular system. Journal of Endodontics, 37(12), 1624-1629.Gazivoda, D., Dzopalic, T., Bozic, B., Tatomirovic, Z., Brkic, Z., & Colic, M. (2009). Pro-duction of proinflammatory and immunoregulatory cytokines by inflammatory cells from periapical lesions in culture. Journal of oral pathology & medicine, 38(7), 605-611.
  34. Da Rosa, W. L. O., Piva, E., & Da Silva, A. F. (2018). Disclosing the physiology of pulp tissue for vital pulp therapy. International Endodontic Journal, 51(8), 829-846.
  35. Dame, Z. T., Aziat, F., Mandal, R., Krishnamurthy, R., Bouatra, S., Borzouie, S., ... & Wishart, D. S. (2015). The human saliva metabolome. Metabolomics, 11, 1864-1883.
  36. Dezerega, A., Madrid, S., Mundi, V., Valenzuela, M. A., Garrido, M., Paredes, R., ... & Hernández, M. (2012). Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response. Journal of Inflammation, 9, 1-9.
  37. Dincer, G. A., Erdemir, A., & Kisa, U. (2020). Comparison of neurokinin A, substance P, interleukin 8, and mat-rix metalloproteinase-8 changes in pulp tissue and gingival crevicular fluid samples of healthy and symptomatic irreversible pulpitis teeth. Journal of Endodontics, 46(10), 1428-1437.
  38. Donnermeyer, D., Dammaschke, T., Lipski, M., & Schäfer, E. (2022). Effectiveness of diagnosing pulpitis: A systematic review. International Endodontic Journal, 1-30.
  39. Duncan HF, Cooper PR, Smith AJ (2019) Dissecting dentinepulp injury and wound healing responses: consequ-ences for regenerative endodontics. International Endodontic Journal 52, 261–6.
  40. Džopalić, T., Tomić, S., Bekić, M., Vu􀀂ević, D., Mihajlović, D., Eraković, M., & 􀀁olić, M. (2022). Ex vivo study of IL-6 expression and function in immune cell subsets from human periapical lesions. International Endodontic Journal, 55(5), 480-494.
  41. El Karim, I. A., Lamey, P. J., Linden, G. J., Awawdeh, L. A., & Lundy, F. T. (2006). Caries-induced changes in the expression of pulpal neuropeptide Y. European Journal of Oral Sciences, 114(2), 133-137.
  42. Elsalhy, M., Azizieh, F., & Raghupathy, R. (2013). Cytokines as diagnostic markers of pulpal inflammation. International endodontic journal, 46(6), 573-580.
  43. Emilia, E., & Neelakantan, P. (2015). Biomarkers in the dentin-pulp complex: role in health and disease. Jour-nal of Clinical Pediatric Dentistry, 39(2), 94-99.
  44. Ersahan, S., Ozcelik, F., Sirin, D. A., Hepsenoglu, Y. E., Ozcelik, I. K., & Topbas, C. (2022). Is adrenomedullin upregulation due to apical periodontitis independent of periodontal disease Odontology, 1-11.
  45. ESE (2019) European society of endodontology position statement: management of deep caries and the expo-sed pulp. International Endodontic Journal 52, 923–34.
  46. Esposito, P., Varvara, G., Caputi, S., & Perinetti, G. (2003). Catalase activity in human healthy and inflamed dental pulps. International Endodontic Journal, 36(9), 599-603.
  47. Fan, R., Sun, B., Zhang, C. F., XUAN, W., WANG, Q. Q., & YIN, X. Z. (2011). Receptor activator of nuclear factor kappa B ligand and osteoprotegerin expression in chronic apical periodontitis: possible association with inflammatory cells. Chinese Medical Journal, 124(14), 2162-2166.
  48. Feridouni Khamaneh, Y., Kiani, P., Miller, R. D., Schlüter, H., & Friedrich, R. E. (2021). Complementing the pulp proteome via sampling with a picosecond infrared laser (PIRL). Clinical Oral Investigations, 25, 6757-6768.
  49. Ferreira, L. G. V., Rosin, F. C. P., & Corrêa, L. (2016). Analysis of Interleukin 17A in periapical abscess and granuloma lesions. Brazilian oral research, 30, e34.
  50. Georgiou, A. C., Twisk, J. W., Crielaard, W., Ouwerling, P., Schoneveld, A. H., & van der Waal, S. V. (2023). The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: A prospective case–control study. International Endodontic Journal, 56(2), 130-145.
  51. Goodman, S. C., Letra, A., Dorn, S., Araujo-Pires, A. C., Vieira, A. E., de Souza, L. C., ... & Silva, R. M. (2014). Expression of heat shock proteins in periapical granulomas. Journal of endodontics, 40(6), 830-836.
  52. Guan, X., He, Y., Wei, Z., Shi, C., Li, Y., Zhao, R., ... & Yang, J. (2021). Crosstalk between Wnt/β-catenin signa-ling and NF-κB signaling contributes to apical periodontitis. International immunopharmacology, 98, 107843.
  53. Gusman, H., Santana, R. B., & Zehnder, M. (2002). Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps. European Journal of Oral ciences, 110(5), 353-357.
  54. Hahn, C. L., & Falkler Jr, W. A. (1992). Antibodies in normal and diseased pulps reactive with microorganisms isolated from deep caries. Journal of Endodontics, 18(1), 28-31.
  55. He, W., Wang, Z., Luo, Z., Yu, Q., Jiang, Y., Zhang, Y., et al. (2015). LPS Promote the Odontoblastic Diffe-rentiation of Human Dental Pulp Stem Cells via MAPK Signaling Pathway. Journal of Cell Physiology. 230, 554–561. Henriques LC, De Brito LC, Tavares WL, Vieira LQ, Ribeiro Sobrinho AP (2011) Cytokine analysis in lesions refractory to endodontic treatment. Journal of Endodontics 37, 1659–62.
  56. Hernández, M., Martínez, B., Tejerina, J. M., Valenzuela, M. A., & Gamonal, J. (2007). MMP-13 and TIMP-1 determinations in progressive chronic periodontitis. Journal of clinical periodontology, 34(9), 729-735.
  57. Hirai, K., Furusho, H., Kawashima, N., Xu, S., de Beer, M. C., Battaglino, R., ... & Sasaki, H. (2019). Serum amyloid A contributes to chronic apical periodontitis via TLR2 and TLR4. Journal of dental research, 98(1), 117-125.
  58. Huang, G. T. J., Potente, A. P., Kim, J. W., Chugal, N., & Zhang, X. (1999). Increased interleukin-8 expression in inflamed human dental pulps. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodon-tology, 88(2), 214-220.
  59. Inchingolo, F., Marrelli, M., Annibali, S., Cristalli, M. P., Dipalma, G., Inchingolo, A. D., ... & Tatullo, M. (2014). Influence of endodontic treatment on systemic oxidative stress. International journal of medical scien-ces, 11(1), 1.
  60. Ishida, M., & Amano, S. (2004). Osteocalcin fragment in bone matrix enhances osteoclast maturation at a late stage of osteoclast differentiation. Journal of Bone and Mineral Metabolism, 22, 415-429.
  61. Izumi, T., Kobayashi, I., Okamura, K., & Sakai, H. (1995). Immunohistochemical study on the immunocompe-tent cells of the pulp in human non-carious and carious teeth. Archives of oral biology, 40(7), 609-614.
  62. Karapanou, V., Kempuraj, D., & Theoharides, T. C. (2008). Interleukin-8 is increased in gingival crevicular fluid from patients with acute pulpitis. Journal of Endodontics, 34(2), 148-151.
  63. Kaur, B., Kobayashi, Y., Cugini, C., & Shimizu, E. (2021). A Mini Review: The Potential Biomarkers for Non-invasive Diagnosis of Pulpal Inflammation. Frontiers in Dental Medicine, 2, 718445.
  64. Kettering, J. D., & Torabinejad, M. (1984). Concentrations of immune complexes, IgG, IgM, IgE, and C3 in patients with acute apical abscesses. Journal of Endodontics, 10(9), 417-421.
  65. Kim, J. C., Lee, Y. H., Yu, M. K., Lee, N. H., Park, J. D., Bhattarai, G., & Yi, H. K. (2012). Anti-inflammatory mechanism of PPARγ on LPS-induced pulp cells: role of the ROS removal activity. Archives of Oral Biology, 57(4), 392-400.
  66. Kim, J., Xin, X., Moioli, E., Chung, J., Lee, C., Chen, M., & Mao, J. (2010). Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Engineering Part A, 16(10), 3023–3031.
  67. Kokkas, A. B., Goulas, A., Varsamidis, K., Mirtsou, V., Tziafas, D. (2007). Irreversible but not reversible pulpi-tis is associated with upregulation of tumour necrosis factoralpha gene expression in human pulp. International Endodontic Journal, 40(3), 198-203.
  68. Lee, H., Bae, A., Kim, J., & Kingsley, K. (2023). Differential Effects of Extracellular Matrix Glycoproteins Fibronectin and Laminin-5 on Dental Pulp Stem Cell Phenotypes and Responsiveness. Journal of Functional Biomaterials, 14(2), 91.
  69. Leonardi, R., Caltabiano, R., & Loreto, C. (2005). Collagenase-3 (MMP-13) is expressed in periapical lesions: an immunohistochemical study. International Endodontic Journal, 38(5), 297-301.
  70. Lepinski, A. M., Hargreaves, K. M., Goodis, H. E., & Bowles, W. R. (2000). Bradykinin levels in dental pulp by microdialysis. Journal of endodontics, 26(12), 744-747.
  71. Li, M., Tian, J., Xu, Z., Zeng, Q., Chen, W., Lei, S., & Wei, X. (2021). Histology-based profile of inflammatory mediators in experimentally induced pulpitis in a rat model: screening for possible biomarkers. International Endodontic Journal, 54(8), 1328-1341.
  72. Loureiro, C., Buzalaf, M. A. R., Moraes, F. R. N., Ventura, T. M. O., Pelá, V. T., Pessan, J. P., Jacinto, R. D. C. (2021). Quantitative proteomic analysis in symptomatic and asymptomatic apical periodontitis. International Endodontic Journal, 54(6), 834-847.
  73. Loureiro, C., Buzalaf, M. A. R., Ventura, T. M. O., Pelá, V. T., Rodrigues, G. W. L., Andrade, J. G., Jacinto, R. C. (2023). Teeth with acute apical abscess vs. teeth with chronic apical periodontitis: a quantitative and quali-tative proteomic analysis. Clinical Oral Investigations, 27(2), 591-601.
  74. Lundy, F. T., Irwin, C. R., McLean, D. F., Linden, G. J., & El Karim, I. A. (2020). Natural antimicrobials in the dental pulp. Journal of Endodontics, 46(9), S2-S9. Márion, I., Kiss, C., Balla, G., Szabó, T., & Karmazsin, L. (1988). Acute phase proteins in patients with chronic periapical granuloma before and after surgical treatment. Oral Microbiology and Immunology, 3(2), 95-96.
  75. Martín-González, J., Pérez-Pérez, A., Cabanillas-Balsera, D., Vilariño-García, T., Sánchez-Margalet, V., & Se-gura-Egea, J. J. (2019). Leptin stimulates DMP-1 and DSPP expression in human dental pulp via MAPK 1/3 and PI3K signaling pathways. Archives of Oral Biology, 98, 126-131.
  76. Marton, I. J., & Kiss, C. (1992). Influence of surgical treatment of periapical lesions on serum and blood levels of inflammatory mediators. International Endodontic Journal, 25(5), 229-233.
  77. Márton, I. J., & Kiss, C. (2014). Overlapping protective and destructive regulatory pathways in apical periodon-titis. Journal of Endodontics, 40(2), 155-163.
  78. Mathieu, S., Jeanneau, C., Sheibat-Othman, N., Kalaji, N., Fessi, H., & About, I. (2013). Usefulness of cont-rolled release of growth factors in investigating the early events of dentin-pulp regeneration. Journal of Endo-dontics, 39(2), 228–235.
  79. Matlashenko, L. A. (1968). The influence of chronic odontogenous infection of the blood serum proteinogram in rheumatic patients. Stomatologiia, 47(2), 8-11.
  80. McClanahan SB, Turner DW, Kaminski EJ, Osetek EM, Heuer MA (1991) Natural modifiers of the inflamma-tory process in the human dental pulp. Journal of Endodontics, 17(12):589–593.
  81. Menezes, R., Garlet, T. P., Letra, A., Bramante, C. M., Campanelli, A. P., de Cássia Figueira, R., Garlet, G. P. (2008). Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: possible association with progressive or stable nature of the lesions. Journal of Endodontics, 34(8), 932-938.
  82. Montis, N., Cotti, E., Noto, A., Fattuoni, C., & Barberini, L. (2019). Salivary metabolomics fingerprint of chro-nic apical abscess with sinus tract: A pilot study. The Scientific World Journal, 3162063.
  83. Morimoto, T., Yamasaki, M., Nakata, K., Tsuji, M., & Nakamura, H. (2008). The expression of macrophage and neutrophil elastases in rat periradicular lesions. Journal of Endodontics, 34(9), 1072-1076.
  84. Mullane, E. M., Dong, Z., Sedgley, C. M., Hu, J. C., Botero, T. M., Holland, G. R., & Nör, J. E. (2008). Effe-cts of VEGF and FGF2 on the revascularization of severed human dental pulps. Journal of Dental Research, 87(12), 1144-1148.
  85. Nakanishi, T., Matsuo, T., & Ebisu, S. (1995). Quantitative analysis of immunoglobulins and inflammatory factors in human pulpal blood from exposed pulps. Journal of Endodontics, 21(3), 131-136.
  86. Naruse, H., Itoh, S., Itoh, Y., Kagioka, T., Abe, M., & Hayashi, M. (2021). The Wnt/β-catenin signaling pat-hway has a healing ability for periapical periodontitis. Scientific Reports, 11(1), 19673.
  87. Nazar Majeed, Z., Philip, K., Alabsi, A. M., Pushparajan, S., & Swaminathan, D. (2016). Identification of gingival crevicular fluid sampling, analytical methods, and oral biomarkers for the diagnosis and monitoring of periodontal diseases: A systematic review. Disease markers, 2016.
  88. Nguyen, V., Chen, Y. W., Johnson, J. D., & Paranjpe, A. (2020). In vivo evaluation of effect of preoperative ibuprofen on proinflammatory mediators in irreversible pulpitis cases. Journal of Endodontics, 46(9), 1210-1216.
  89. Nikolic, N., Jakovljevic, A., Carkic, J., Beljic-Ivanovic, K., Miletic, M., Soldatovic, I., ... & Milasin, J. (2019). Notch signaling pathway in apical periodontitis: correlation with bone resorption regulators and proinflamma-tory cytokines. Journal of Endodontics, 45(2), 123-128.
  90. Nireeksha, Varma, S. R., Damdoum, M., Alsaegh, M. A., Hegde, M. N., Kumari, S. N., ... & Khurshid, Z. (2021). Immunomodulatory expression of cathelicidins peptides in pulp inflammation and regeneration: an update. Current Issues in Molecular Biology, 43(1), 116-126.
  91. Nogueıra, E. F. D. C., Farıas, E. G. F., Sılva, L. B., Santos Neto, A. P. D., Andrade, E. S. D. S., & Sampaıo, G. C. (2016). Analysis of the presence and location of mast cells in periapical cysts and periapical granulomas. RGO-Revista Gaúcha de Odontologia, 64, 376-381.
  92. Nuti, N., Corallo, C., Chan, B. M. F., Ferrari, M., & Gerami-Naini, B. (2016). Multipotent differentiation of human dental pulp stem cells: a literature review. Stem Cell Reviews and Reports, 12, 511-523. Ornitz, D. M., & Itoh, N. (2015). The fibroblast growth factor signaling pathway. Wiley Interdisciplinary Re-views Developmental Biology, 4(3), 215–266.
  93. Paris, S., Wolgin, M., Kielbassa, A. M., Pries, A., & Zakrzewicz, A. (2009). Gene expression of human beta-de-fensins in healthy and inflamed human dental pulps. Journal of Endodontics, 35(4), 520-523.
  94. Pattamapun, K., Handagoon, S., Sastraruji, T., Gutmann, J. L., Pavasant, P., & Krisanaprakornkit, S. (2017). Decreased levels of matrix metalloproteinase-2 in root-canal exudates during root canal treatment. Archives of Oral Biology, 82, 27-32.
  95. Pezelj-Ribaric, S., Anic, I., Brekalo, I., Miletic, I., Hasan, M., & Simunovic-Soskic, M. (2002). Detection of tumor necrosis factor α in normal and inflamed human dental pulps. Archives of Medical Research, 33(5), 482-484.
  96. Piattelli, A., Rubini, C., Fioroni, M., Tripodi, D., & Strocchi, R. (2004). Transforming Growth Factor-beta 1 (TGF-beta 1) expression in normal healthy pulps and in those with irreversible pulpitis. International Endodon-tic Journal, 37(2), 114-119.
  97. Proctor, M. E., Turner, D. W., Kaminski, E. J., Osetek, E. M., & Heuer, M. A. (1991). Determination and re-lationship of C-reactive protein in human dental pulps and in serum. Journal of Endodontics, 17(6), 265-270.
  98. Provenzano, J. C., Siqueira Jr, J. F., Rocas, I. N., Domingues, R. R., Paes Leme, A. F., & Silva, M. R. (2013). Metaproteome analysis of endodontic infections in association with different clinical conditions. PLoS One, 8(10), e76108.
  99. Rauschenberger, C. R., Bailey, J. C., Cootauco, C. J. (1997). Detection of human IL-2 in normal and inflamed dental pulps. Journal of Endodontics, 23(6), 366-370.
  100. Rauschenberger, C. R., McClanahan, S. B., Pederson, E. D., Turner, D. W., & Kaminski, E. J. (1994). Com-parison of human polymorphonuclear neutrophil elastase, polymorphonuclear neutrophil cathepsin-G, and α2-macroglobulin levels in healthy and inflamed dental pulps. Journal of Endodontics, 20(11), 546-549.
  101. Rechenberg, D. K., Bostanci, N., Zehnder, M., & Belibasakis, G. N. (2014). Periapical fluid RANKL and IL-8 are differentially regulated in pulpitis and apical periodontitis. Cytokine, 69(1), 116-119.
  102. Rechenberg, D. K., Galicia, J. C., & Peters, O. A. (2016). Biological markers for pulpal inflammation: a syste-matic review. PloS one, 11(11), e0167289.
  103. Resch, Z. T., Chen, B. K., Bale, L. K., Oxvig, C., Overgaard, M. T., & Conover, C. A. (2004). Pregnancy-associ-ated plasma protein a gene expression as a target of inflammatory cytokines. Endocrinology, 145(3), 1124-1129.
  104. Rodd HD, Boissonade FM. Substance P expression in human tooth pulp in relation to caries and pain experien-ce. Eur J Oral Sci 2000;108:467–74.
  105. Rubartelli, A., & Lotze, M. T. (2007). Inside, outside, upside down: damage-associated molecular-pattern mo-lecules (DAMPs) and redox. Trends in Immunology, 28(10), 429-436.
  106. Sakagami, H., Nakatani, S., Enomoto, A., Ota, S., Kaneko, M., Sugimoto, M., ... & Oizumi, T. (2021). Mul-ti-Omics Analysis of Anti-Inflammatory Action of Alkaline Extract of the Leaves of Sasa sp. Journal of Clinical Medicine, 10(10), 2100.
  107. Sambandam, V., & Neelakantan, P. (2014). Matrix metalloproteinases (mmp) in restorative dentistry and endo-dontics. Journal of Clinical Pediatric Dentistry, 39(1), 57-59.
  108. Sasaki, R., Aoki, S., Yamato, M., Uchiyama, H., Wada, K., Okano, T., & Ogiuchi, H. (2008). Neurosphere ge-neration from dental pulp of adult rat incisor. European Journal of Neuroscience, 27(3), 538–548.
  109. Sattari, M., Haghighi, A. K., & Tamijani, H. D. (2009). The relationship of pulp polyp with the presence and concentration of immunoglobulin E, histamine, interleukin-4 and interleukin-12. Australian Endodontic Jour-nal, 35(3), 164-168.
  110. Sharma, R., Kumar, V., Logani, A., Chawla, A., Mir, R. A., Sharma, S., & Kalaivani, M. (2021). Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis–a preliminary study. International Endodontic Journal, 54(4), 479-489.
  111. Shen, Z., & Silva, R. M. (2021). MicroRNAs: emerging players in apical periodontitis. Journal of Applied Oral Science, 29. Shimabukuro, Y., Ueda, M., Ichikawa, T., Terashi, Y., Yamada, S., Kusumoto, Y.,Murakami, S. (2005). Fibrob-last growth Factor-2 stimulates hyaluronan production by human dental pulp cells. Journal of Endodontics, 31(11), 805–808.
  112. Shin, S. J., Lee, J. I., Baek, S. H., & Lim, S. S. (2002). Tissue levels of matrix metalloproteinases in pulps and periapical lesions. Journal of Endodontics, 28(4), 313-315.
  113. Shin, S. J., Lee, J. I., Baek, S. H., & Lim, S. S. (2002). Tissue levels of matrix metalloproteinases in pulps and periapical lesions. Journal of Endodontics, 28(4), 313-315.
  114. Silva, A. C. O., Faria, M. R., Fontes, A., Campos, M. S., & Cavalcanti, B. N. (2009). Interleukin-1 beta and interleukin-8 in healthy and inflamed dental pulps. Journal of Applied Oral Science, 17, 527-532.
  115. Silva, M. J. B., Sousa, L. M. A., Lara, V. P. L., Cardoso, F. P., Júnior, G. M., Totola, A. H., ... & Vieira, L. Q. (2011). The role of iNOS and PHOX in periapical bone resorption. Journal of dental research, 90(4), 495-500.
  116. Silva, P. A. O., Lima, S. M. D. F., Freire, M. D. S., Murad, A. M., Franco, O. L., & Rezende, T. M. B. (2021). Proteomic analysis of human dental pulp in different clinical diagnosis. Clinical Oral Investigations, 25, 3285-3295.
  117. Sirin, D. A., Ozcelik, F., Ersahan, S., & Pence, H. H. (2021). The importance of inflammatory biomarkers, IL-6 and PAPP-A, in the evaluation of asymptomatic apical periodontitis. Odontology, 109, 250-258.
  118. Soundararajan, M., & Kannan, S. (2018). Fibroblasts and mesenchymal stem cells: Two sides of the same coin? Journal of Cellular Physiology, 233(12), 9099-9109.
  119. Sousa, E. L., Martinho, F. C., Leite, F. R., Nascimento, G. G., & Gomes, B. P. (2014). Macrophage cell ac-tivation with acute apical abscess contents determined by interleukin-1 Beta and tumor necrosis factor alpha production. Journal of Endodontics, 40(11), 1752-1757.
  120. Stabholz, A., & McArthur, W. P. (1978). Cellular immune response of patients with periapical pathosis to nec-rotic dental pulp antigens determined by release of LIF. Journal of Endodontics, 4(9), 282-287.
  121. Strimbu, K., & Tavel, J. A. (2010). What are biomarkers? Current Opinion in HIV and AIDS, 5(6), 463.
  122. Sui, B., Wu, D., Xiang, L., Fu, Y., Kou, X., & Shi, S. (2020). Dental pulp stem cells: from discovery to clinical application. Journal of Endodontics, 46(9), S46-S55.
  123. Svetcov, S. D., DeAngelo, J. E., McNamara, T., & Nevins, A. J. (1983). Serum immunoglobulin levels and bacterial flora in subjects with acute oro-facial swellings. Journal of Endodontics, 9(6), 233-235.
  124. Trombone, A. P. F., Cardoso, C. R., Repeke, C. E., Ferreira Jr, S. B., Martins Jr, W., Campanelli, A. P., Garlet, G. P. (2009). Tumor necrosis factor-alpha− 308G/A single nucleotide polymorphism and red-complex periodonto-pathogens are independently associated with increased levels of tumor necrosis factor-α in diseased periodontal tissues. Journal of Periodontal Research, 44(5), 598-608.
  125. Tuncer, L. I., Alaçam, T., & Oral, B. (2004). Substance P expression is elevated in inflamed human periradicular tissue. Journal of Endodontics, 30(5), 329-332.
  126. Uddman, R., Grunditz, T., & Sundler, F. (1984). Neuropeptide Y: occurrence and distribution in dental pulps. Acta Odontologica Scandinavica, 42(6), 361-365.
  127. Wahlgren, J., Salo, T., Teronen, O., Luoto, H., Sorsa, T., & Tjäderhane, L. (2002). Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root-canal exudates. International Endodontic Journal, 35(11), 897-904.
  128. Wang, C. Y., Tani-Ishii, N., & Stashenko, P. (1997). Bone-resorptive cytokine gene expression in periapical lesions in the rat. Oral microbiology and immunology, 12(2), 65-71.
  129. Wei, X. L., Luo, L., Chen, M. Z., Zhou, J., Lan, B. Y., Ma, X. M., & Chen, W. X. (2023). Temporospatial exp-ression of neuropeptide substance P in dental pulp stem cells during odontoblastic differentiation in Vitro and reparative dentinogenesis in Vivo. Journal of Endodontics, 49(3), 276-285.
  130. Yang, X., Van der Kraan, P. M., Dolder, J. V. D., Walboomers, X. F., Bian, Z., Fan, M., & Jansen, J. A. (2007). STRO-1 selected rat dental pulp stem cells transfected with adenoviral-mediated human bone morphogenetic protein 2 gene show enhanced odontogenic differentiation. Tissue Engineering, 13(11), 2803-2812. Yianni, V., & Sharpe, P. T. (2020). Transcriptomic profiling of dental pulp pericytes: an RNAseq approach. Frontiers in Dental Medicine, 1, 6.
  131. Yue, J., Song, D., Lu, W., Lu, Y., Zhou, W., Tan, X., ... & Huang, D. (2016). Expression profiles of inflamma-tion-associated microRNAs in periapical lesions and human periodontal ligament fibroblasts inflammation. Journal of Endodontics, 42(12), 1773-1778.
  132. Yue, J., Wang, P., Hong, Q., Liao, Q., Yan, L., Xu, W., ... & Huang, D. (2017). MicroRNA-335-5p plays dual roles in periapical lesions by complex regulation pathways. Journal of Endodontics, 43(8), 1323-1328.
  133. Zehnder, M., & Belibasakis, G. N. (2022). A critical analysis of research methods to study clinical molecular biomarkers in Endodontic research. International Endodontic Journal, 55, 37-45.
  134. Zehnder, M., Delaleu, N., Du, Y., & Bickel, M. (2003). Cytokine gene expression—part of host defence in pulpitis. Cytokine, 22(3-4), 84-88.
  135. Zehnder, M., Delaleu, N., Du, Y., & Bickel, M. (2003). Cytokine gene expression—part of host defence in pulpitis. Cytokine, 22(3-4), 84-88.
  136. Zehnder, M., Wegehaupt, F. J., & Attin, T. (2011). A first study on the usefulness of matrix metalloproteinase 9 from dentinal fluid to indicate pulp inflammation. Journal of Endodontics, 37(1), 17-20.
  137. Zhong, S., Zhang, S., Bair, E., Nares, S., & Khan, A. A. (2012). Differential expression of microRNAs in nor-mal and inflamed human pulps. Journal of Endodontics, 38(6), 746-752.