Decoding the Biochemical Pathways of Orthodontic Tooth Movement: A Focus on Salivary IL-17A and 1,25-Dihydroxycholecalciferol

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DOI: 10.21522/TIJPH.2013.13.02.Art092

Authors : Sandra Sagar, Selvaraj Jayaraman, Pratibha Ramani, Genickson Jeyaraj, Sagar Moses

Abstract:

Orthodontic treatment leads to significant alterations in the oral environment, including changes in salivary biomarker levels. Among these, interleukin-17A (IL-17A) and 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃) play crucial roles in immune regulation and bone metabolism, respectively. IL-17A is a proinflammatory cytokine involved in immune responses and bone remodelling, while 1,25(OH)₂D₃, the active form of vitamin D, influences calcium homeostasis and skeletal health. Understanding the dynamic interplay between these biomarkers during orthodontic treatment may provide valuable insights into the biological mechanisms underlying inflammation and bone remodelling. This review systematically examines existing literature on the correlation between salivary IL-17A and 1,25(OH)₂D₃ levels in patients undergoing orthodontic interventions. By analyzing studies that investigate these biomarkers, this paper aims to elucidate their role in orthodontic-induced bone remodelling and inflammatory responses. Identifying potential patterns in their expression may help predict treatment outcomes and assess patient-specific variations in response to orthodontic forces. Furthermore, this review highlights the clinical implications of monitoring salivary IL-17A and 1,25(OH)₂D₃ levels, as fluctuations in these biomarkers could serve as indicators of treatment progress and tissue adaptation. A deeper understanding of these biochemical interactions may contribute to optimizing orthodontic treatment strategies and developing novel therapeutic approaches to enhance patient care. By bridging the gap between orthodontics and molecular biology, this review provides a foundation for future research exploring personalized treatment plans based on biomarker profiling.

References:

[1].   Phulari, B. S., 2013, History of Orthodontics. JP Medical Ltd.

[2].   Davidovitch, Z., Krishnan, V., 2009, Role of basic biological sciences in clinical orthodontics: a case series. Am J Orthod Dentofacial Orthop, 135:222–31.

[3].   Krishnan, V., Kuijpers-Jagtman, A. M., Davidovitch, Z., 2021, Biological Mechanisms of Tooth Movement. John Wiley & Sons.

[4].   Sagar, S., Ramani, P., Moses, S., Gheena, S., Selvaraj, J., 2024, Correlation of salivary cytokine IL-17A and 1,25 dihydroxycholecalciferol in patients undergoing orthodontic treatment. Odontology, 112(3):966-975. Doi: 10.1007/s10266-023-00890-1. Epub 2024 Feb 6. PMID: 38319548.

[5].   Sandy, J. R., Farndale, R. W., Meikle, M. C., 1993, Recent advances in understanding mechanically induced bone remodeling and their relevance to orthodontic theory and practice. Am J Orthod Dentofacial Orthop, 103:212–22. https://doi.org/10.1016/0889-5406(93)70002-6

[6].   Krishnan, V., Davidovitch, Z., 1993, Biological Mechanisms of Tooth Movement. John Wiley & Sons, 2009.

[7].   Ellias, M. F., Zainal Ariffin, S. H., Karsani, S. A., Abdul Rahman, M., Senafi, S., Megat Abdul Wahab, R., 2012, Proteomic analysis of saliva identifies potential biomarkers for orthodontic tooth movement. Sci World J, https://doi.org/10.1100/2012/647240

[8].   Oppenheim, A., 2007, Tissue changes, particularly of the bone, incident to tooth movement. Eur J Orthod, 29: i2–15. https://doi.org/10.1093/ejo/cjl105

[9].   Kaczor-Urbanowicz, K. E., Deutsch, O., Zaks, B., Krief, G., Chaushu, S., Palmon, A., 2017, Identification of salivary protein biomarkers for orthodontically induced inflammatory root resorption. Proteomics Clin Appl, 11:9-10. https://doi.org/10.1002/prca.201600119

[10].  Grimm, F. M., 1972, Bone bending, a feature of orthodontic tooth movement. Am J Orthod, 62:384–93. https://doi.org/10.1016/s0002-9416(72)90278-3

[11].  Schwarz, A. M., Martin Schwarz, A., 1932, Tissue changes incidental to orthodontic tooth movement. Int J Orthodont Oral Surg Radiogr, 18:331–52. https://doi.org/10.1016/s0099-6963(32)80074-8

[12].  Kardos, T. B., Simpson, L. O., 1980, A new periodontal membrane biology based upon thixotropic concepts. Am J Orthod, 77:508–15.

[13].  Yee, J. A., Kimmel, D. B., Jee, W. S., 1976, Periodontal ligament cell kinetics following orthodontic tooth movement. Cell Tissue Kinet, 9:293–302.

[14].  Reitan, K., 1957, Some factors determining the evaluation of forces in orthodontics. Am J Orthod, 43:32–45. https://doi.org/10.1016/0002-9416(57)90114-8

[15].  Alhashimi, N., Frithiof, L., Brudvik, P., Bakhiet, M., 2000, Orthodontic movement induces high numbers of cells expressing IFN-gamma at mRNA and protein levels. J Interferon Cytokine Res, 20:7–12. https://doi.org/10.1089/107999000312685

[16].  Alhashimi, N., Frithiof, L., Brudvik, P., Bakhiet, M., 2001, Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines. Am J Orthod Dentofacial Orthop, 119:307–12.

[17].  Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Lüthy, R., et al., 1997, Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 89:309–19.

[18].  Senthil, R., 2025,  Formation of bone tissue apatite on starch-based nanofiber-capped nanohydroxyapatite and reduced graphene oxide: a preliminary study. Oral Maxillofac Surg 29, 6. https://doi.org/10.1007/s10006-024-01303-5

[19].  Gul, S. S., Abdulkareem, A. A., Sha, A. M., Rawlinson, A., 2020, Diagnostic accuracy of oral fluids biomarker profile to determine the current and future status of periodontal and peri-implant diseases. Diagnostics (Basel), 10. https://doi.org/10.3390/diagnostics10100838

[20].  Justino, A. B., Teixeira, R. R., Peixoto, L. G., Jaramillo, O. L. B., Espindola, F. S., 2017, Effect of saliva collection methods and oral hygiene on salivary biomarkers. Scand J Clin Lab Invest, 77:415–422.

[21].  Humphrey, S. P., Williamson, R. T., 2001, A review of saliva: normal composition, flow, and function. J Prosthet Dent, 85:162–9.

[22].  Bonne, N. J., Wong, D. T. W., 2012, Salivary biomarker development using genomic, proteomic, and metabolomic approaches. Genome Med, 4:1–12.

[23].  Allen, R. K., Edelmann, A. R., Abdulmajeed, A., Bencharit, S., 2019, Salivary protein biomarkers associated with orthodontic tooth movement: A systematic review. Orthod Craniofac Res, 22 Suppl 1:14–20.

[24].  Navarro-Palacios, A., García-López, E., Meza-Rios, A., Armendariz-Borunda, J., Sandoval-Rodríguez, A., 2014, Myeloperoxidase enzymatic activity is increased in patients with different levels of dental crowding after initial orthodontic activation. Am J Orthod Dentofacial Orthop, 146:92–7.

[25].  Flórez-Moreno, G. A., Isaza-Guzmán, D. M., Tobón-Arroyave, S. I., 2013, Time-related changes in salivary levels of the osteotropic factors sRANKL and OPG through orthodontic tooth movement. Am J Orthod Dentofacial Orthop, 143:92–100.

[26].  Tuncer, B. B., Ozmeriç, N., Tuncer, C., Teoman, I., Cakilci, B., Yücel, A., et al., 2005, Levels of interleukin-8 during tooth movement. Angle Orthod, 75:631–6.

[27].  Deeksheetha, P., Ramalingam, K., Ramani, P., Jayaraman, S., Akilarooran, A., 2025, Insulin receptor substrate 1 (IRS 1) serum levels in patients with oral squamous cell carcinoma. Oral Oncol Rep, 1:100708. https://doi.org/10.1016/j.oor.2024.100708

[28].  Garlet, T. P., Coelho, U., Silva, J. S., Garlet, G. P., 2007, Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans. Eur J Oral Sci, 115:355–62.https://doi.org/10.1111/j.1600-0722.2007.00469.x

[29].  Harris JJ, Rajasekar A., 2025, Efficacy of antimicrobial photodynamic therapy (a-PDT) as an adjunct to scaling and root planing on clinical parameters, oxidative and anti-oxidative profile in the treatment of chronic periodontitis: a randomized controlled clinical trial. Odontology, Epub ahead of print. doi: 10.1007/s10266-025-01106-4. 

[30].  Kennedy, J., Rossi, D. L., Zurawski, S. M., Vega, F. Jr., Kastelein, R. A., Wagner, J. L., et al., 1996, Mouse IL-17: a cytokine preferentially expressed by alpha beta TCR+ CD4-CD8-T cells. J Interferon Cytokine Res., 16:611–7.

[31].  Taylor, P. R., Roy, S., Leal, S. M. Jr., Sun, Y., Howell, S. J., Cobb, B. A., et al., 2014, Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt, and dectin-2. Nat Immunol, 15:143–51.

[32].  Sagar, S., Ramani, P., Yuwanati, M., Moses, S., Ramalingam, K., 2023, Role of 1,25-dihydroxycholecalciferol on the acceleration of orthodontic tooth movement: A systematic review. Int J Orthod Rehabil, 14(4):19–32. https://doi.org/10.56501/intjorthodrehabil.v14i4.877

[33].  Senthil R, Çakır S., 2024. Nano apatite growth on demineralized bone matrix capped with curcumin and silver nanoparticles: Dental implant mechanical stability and optimal cell growth analysis. J Oral Biosci., 66(1):232-240. doi: 10.1016/j.job.2023.12.004.

[34].  Carlberg, C., 2014, Genome-wide view on the physiology of vitamin D. Front E-books.

[35].  Yetley, E. A., Brulé, D., Cheney, M. C., Davis, C. D., Esslinger, K. A., Fischer, P. W. F., et al., 2009, Dietary reference intakes for vitamin D: Justification for a review of the 1997 values. Am J Clin Nutr, 89:719–27. https://doi.org/10.3945/ajcn.2008.26903

[36].  Liu, K., Meng, H., Hou, J., 2012, Characterization of the autocrine/paracrine function of vitamin D in human gingival fibroblasts and periodontal ligament cells. PLoS ONE, 7: e39878. https://doi.org/10.1371/journal.pone.0039878

[37].  Collins, M. K., Sinclair, P. M., 1988, The local use of vitamin D to increase the rate of orthodontic tooth movement. Am J Orthod Dentofacial Orthop, 94:278–84.

[38].  Giustina, A., Bilezikian, J. P., 2018, Vitamin D in Clinical Medicine. Karger Med Sci Publ.

[39].  Alagesan, A., Rajendran, K., Raghavan, V., Tirumalasetty, S., Vasanthakumar, V., Reddy, M., 2023, A study of serum vitamin D levels in COVID-19 patients and its association with severity of the disease.

[40].  Sagar, S., Raman, P., Gheena, S., Abilasha, R., Krishnan, R. P., Selvaraj, J., 2022, Salivary vitamin D levels among OSCC and normal Indian patients. Bioinformation, 18(10):884–7. https://doi.org/10.6026/97320630018884