Identification of azurocidin as a potential periodontitis biomarker by a proteomic analysis of gingival crevicular fluid
Open accessAbstract
BACKGROUND: The inflammatory disease periodontitis results in tooth loss and can even lead to diseases of the whole body if not treated. Gingival crevicular fluid (GCF) reflects the condition of the gingiva and contains proteins transuded from serum or cells at inflamed sites. In this study, we aimed to discover potential protein biomarkers for periodontitis in GCF proteome using LC-MS/MS. RESULTS: We identified 305 proteins from GCF of healthy individuals and periodontitis patients collected using a sterile gel loading tip by ESI-MS/MS coupled to nano-LC. Among these proteins, about 45 proteins were differentially expressed in the GCF proteome of moderate periodontitis patients when compared to the healthy individuals. We first identified azurocidin in the GCF, but not the saliva, as an upregulated protein in the periodontitis patients and verified its increased expression during periodontitis by ELISA using the GCF of the classified periodontitis patients compared to the healthy individuals. In addition, we found that azurocidin inhibited the differentiation of bone marrow-derived macrophages to osteoclasts. CONCLUSIONS: Our results show that GCF collection using a gel loading tip and subsequent LC-MS/MS analysis following 1D-PAGE proteomic separation are effective for the analysis of the GCF proteome. Our current results also suggest that azurocidin could be a potential biomarker candidate for the early detection of inflammatory periodontal destruction by gingivitis and some chronic periodontitis. Our data also suggest that azurocidin may have an inhibitory role in osteoclast differentiation and, thus, a protective role in alveolar bone loss during the early stages of periodontitis.
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AZU levels in GCF are significantly higher in patients with chronic periodontitis compared to periodontally healthy patients.
“Significantly higher levels are found in patients with chronic periodontitis compared to periodontally healthy patients”
From Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review (2023) · cites this paper as [155]
The Results section (Verification of azurocidin expression in GCF using ELISA; page unavailable) reports higher GCF azurocidin levels in moderate and severe periodontitis patients than in healthy controls. It gives no azurocidin-specific statistical result establishing that the difference was significant, so the claim’s significance qualifier is not verified. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAZU is involved in the pathogenesis of periodontal disease.
“indicating that this protein is also involved in PD pathogenesis [103,154,155].”
From Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review (2023) · cites this paper as [155]
The Results section reports that azurocidin inhibited osteoclast differentiation, a process relevant to periodontal bone loss. The Discussion suggests azurocidin may protect against bone loss in early periodontitis, but does not establish its role in periodontal disease pathogenesis as a fact. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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BackgroundProteomic Analysis of a PDEF Ets Transcription Factor-Interacting Protein Complex
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MethodInfluentialSelf-citation
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Azurocidin in gingival crevicular fluid as a potential biomarker of chronic periodontitis
Nalmpantis, D., Gatou, A., Fragkioudakis, I., Margariti, A., Skoura, L., & Sakellari, D. (2020) · Journal of Periodontal Research · doi:10.1111/jre.12703 · Cited by 17 · see citing works
Bellei, E., Bertoldi, C., Monari, E., & Bergamini, S. (2022) · Materials · doi:10.3390/ma15062161 · Cited by 18 · see citing works
“In support of our findings, other previous works showed an up-regulation of this protein in the GCF of patients affected by chronic periodontitis in comparison to periodontally healthy subjects [39,40].”
ResultTorres, A., Michea, M., Végvári, Á., Arce, M., Morales, A., Lanyon, E., Alcota, M., Fuentes, C., Vernal, R., Budini, M., et al. (2023) · Journal of Periodontal Research · doi:10.1111/jre.13169 · Cited by 15 · see citing works
Preianò, M., Maggisano, G., Murfuni, M. S., Villella, C., Pelaia, C., Montalcini, T., Lombardo, N., Pelaia, G., Savino, R., & Terracciano, R. (2018) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201800005 · Cited by 16 · see citing works
Antimicrobial peptides and proteins in human biological fluids
Иксанова, А. М., Arzumanian, V. G., Konanykhina, S. Y., & Samoylikov, P. V. (2022) · Microbiology Independent Research Journal (MIR Journal) · doi:10.18527/2500-2236-2022-9-1-37-55 · Cited by 16 · see citing works
Antimicrobial peptide gene expression in periodontitis patients: A pilot study
Jourdain, M., Pierrard, L., Kanagaratnam, L., Velard, F., Sergheraert, J., Lefèvre, B., Gangloff, S. C., & Braux, J. (2018) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12879 · Cited by 16 · see citing works
Mohammed-Salih, H. S., Al-Lami, H. A., Saloom, H. F., Abdulkareem, A. A., Al‐Obaidi, J. R., & Razali, N. (2023) · 3 Biotech · doi:10.1007/s13205-023-03572-5 · Cited by 9 · see citing works
Batschkus, S., Cingoez, G., Urlaub, H., Miosge, N., Kirschneck, C., Meyer-Marcotty, P., & Lenz, C. (2017) · Clinical Oral Investigations · doi:10.1007/s00784-017-2213-0 · Cited by 11 · see citing works
Musiał, N., Bogucka, A. E., Tretiakow, D., Skorek, A., Ryl, J., & Czaplewska, P. (2023) · Clinical Proteomics · doi:10.1186/s12014-023-09402-3 · Cited by 10 · see citing works
“Azurocidin 1 has inhibitory activity during periodontitis, so its variable level can cause different pathological states [82].”
BackgroundXiao, X., Song, T., Xiao, X., Liu, Y., Sun, H., Guo, Z., Liu, X., Shao, C., Li, Q., & Sun, W. (2021) · PROTEOMICS · doi:10.1002/pmic.202000321 · Cited by 11 · see citing works
Blanco‐Pintos, T., Regueira‐Iglesias, A., Relvas, M., Alonso‐Sampedro, M., Chantada‐Vázquez, M. D. P., Balsa‐Castro, C., & Tomás, I. (2024) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.14037 · Cited by 12 · see citing works
Tsuchida, S., Satoh, M., Sogawa, K., Kawashima, Y., Kado, S., Ishige, T., Beppu, M., Sawai, S., Nishimura, M., Kodera, Y., et al. (2014) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201300122 · Cited by 10 · see citing works
“, 2011 1D-PAGE, LC-MS/MS 305 proteins Azurocidin [57] Baliban et al.”
ResultXanthopoulou, V., Räisänen, I. T., Sorsa, T. A., Tortopidis, D., & Sakellari, D. (2024) · Clinical and Experimental Dental Research · doi:10.1002/cre2.883 · Cited by 10 · see citing works
Tracking the functional meaning of the human oral-microbiome protein-protein interactions
Rosa, N. D. N., Campos, B., Esteves, A. C., Duarte, A. S., Correia, M. J., Silva, R. M., & Barros, M. (2020) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.11.014 · Cited by 8 · see citing works
Revolutionizing Periodontic Care: Nano Dentistry's Impact on Inflammation Management
Chaturvedi, A., Gupta, G., Kesharwani, P., & Shukla, R. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.105922 · Cited by 6 · see citing works
Marcantonio, C. C., Lopes, M. E. S., Mofatto, L. S., Salmon, C. R., Deschner, J., Nociti, F. H., Cirelli, J. A., & Nogueira, A. V. B. (2022) · Journal of Proteomics · doi:10.1016/j.jprot.2022.104616 · Cited by 6 · see citing works
Bellei, E., Monari, E., Bertoldi, C., & Bergamini, S. (2024) · Sci · doi:10.3390/sci6040057 · Cited by 6 · see citing works
In silico analyses of heparin binding proteins expression in human periodontal tissues
Lackey, B., Nunes, Q. M., Higham, S. M., Fernig, D. G., & Valappil, S. P. (2016) · BMC Research Notes · doi:10.1186/s13104-016-1857-1 · Cited by 5 · see citing works
“It has been reported that HBPs such as azurocidin could be a potential candidate for a biomarker for the early detection of inflammatory periodontal destruction [6].”
BackgroundResultAlpha-Defensin 1: An Emerging Periodontitis Biomarker
Lee, J., Chang, D., Kim, J., & Hwang, Y. (2023) · Diagnostics · doi:10.3390/diagnostics13132143 · Cited by 3 · see citing works
“Azurocidin is secreted from neutrophils as a lysosomal protein and acts as a multifunctional inflammatory mediator [5].”
BackgroundSelf-citationProteomics - The Future of Periodontal Diagnostics
Kj, N., & George, A. K. (2017) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2017.01.000447 · Cited by 3 · see citing works
“[27] searched for potential protein biomarkers for periodontitis in gingival crevicular fluid using LC tandem MS (LC-MS-MS).”
MethodProteomics of Periodontal Pocket
Sakellari, D. (2017) · Current Oral Health Reports · doi:10.1007/s40496-017-0160-0 · Cited by 3 · see citing works
Proteomics:A New Diagnostic Horizon In Periodontics.
Patil, V., Wagh, P. P., Patel, J. R., Bhargavi, B., & George, B. (2017) · doi:10.9790/0853-1604105257 · Cited by 3
Proteomics or Genomics: A New Era in Periodontics
Khopade, S., Sable, S. D., Happy, D., Hadge, P., & Sayyed, J. (2013) · doi:10.4103/2277-4696.159286 · Cited by 3
Balu, P., Pillai, A. K. B., Sivagnanam, A., Mariappan, V., & Ramalingam, S. (2023) · Gene Reports · doi:10.1016/j.genrep.2023.101845 · Cited by 2 · see citing works
Analysis of Periodontitis Biomarker Expression in Gingival Crevicular Fluids
Hwang, Y. S. (2021) · Journal of dental hygiene science · doi:10.17135/jdhs.2021.21.1.45 · Cited by 2 · see citing works
Hu, J.-Y., Hu, Y., Liu, R., Li, Y., Fu, F., Yu, J., & Ni, Y. (2026) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-026-08896-7 · Cited by 1
“…is not merely upregulated but serves as a specific biomarker reflective of the dysregulated intra-amniotic inflammation that defines CA. Heparin-binding protein (HBP), also known as cationic antibacterial protein 37 (CAP37), is named for its extremely strong Heparin binding ability [14].”
Alarcón‐Sánchez, M. A., Martínez, S. M. L., Montaño, R. R., Becerra‐Ruiz, J. S., Martínez‐Bugarin, C. H., Mosaddad, S. A., & Heboyan, A. G. (2025) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2025.106256 · Cited by 1 · see citing works
Антимикробные пептиды и белки в биожидкостях человека
Иксанова, А. М., Arzumanian, V. G., Konanykhina, S. Y., & Samoilikov, P. V. (2022) · Microbiology Independent Research Journal (MIR Journal) · doi:10.18527/2500-2236-2022-9-1-37-55.ru · Cited by 1 · see citing works
Xw, C., Wu, X., He, C., Huang, Y., Zhang, R., Wu, Q., Chen, Y., Ouyang, J., Yan, L., Lv, Y., et al. (2026) · Current Microbiology · doi:10.1007/s00284-026-05071-1
Souza, L. D. P. S. S., Dias, D. R., Cesar, G. P. S., Bianco, D. D. A., Araújo, M., & Matarazzo, F. (2026) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5c01217
Ahmad, P., Lowe, C., Chumala, P., & Siqueira, W. L. (2025) · The Veterinary Journal · doi:10.1016/j.tvjl.2025.106521
Proteomic Analysis of the Periodontal Ligament During Orthodontic Movement: A Study in Rats
Marcantonio, C. C., Lopes, M. E. S., Soares, L. F. F., Salmon, C., Nociti, F., Deschner, J., Nogueira, A., & Cirelli, J. (2025) · Proteomes · doi:10.3390/proteomes13030042
Characterization of lactoferrin in gingival crevicular fluid of chronic periodontitis patient
Wati, S. M., Istiati, I., & Soesilawati, P. (2014) · doi:10.20473/j.djmkg.v47.i3.p141-145
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- Authors
- Choi, Y.-J., Heo, S.-H., Lee, J.-M., & Cho, J.-Y.
- Affiliations
- Kyungpook National University (KR)
- Corresponding author
- Cho, Je-Yoel
- Venue
- Proteome Science
- Published
- 2011
- Volume
- 9
- Issue
- 1
- Pages
- 42
- ISSN
- 1477-5956 (ISSN-L)
- PMC
- PMC3162872
- OpenAlex
- W2040590695
- Cited by
- 71
- References
- 39
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Proteome Science (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Education, Science and Technology
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- heparin-binding protein, periodontitis, gingival crevicular fluid, biomarkers, proteome, osteoclastogenesis, alveolar bone loss, chronic periodontitis, gingivitis, macrophages
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