Expression of growth mediators in the gingival crevicular fluid of patients with aggressive periodontitis undergoing periodontal surgery

  • T. Rakmanee
  • E. Calciolari
  • I. Olsen
  • U. Darbar
  • G. S. Griffiths
  • A. Petrie
  • Nikolaos DonosEmail author
Original Article



To describe changes in growth factor mediators in the gingival crevicular fluid (GCF) of patients with aggressive periodontitis (AgP) undergoing regenerative (GTR) and access flap (AF) surgery.

Materials and methods

This was a 12-month, single-blind, split-mouth RCT involving 18 AgP patients with a bilateral intrabony defect which was treated with GTR or AF. GCF was collected prior to surgery and at subsequent follow-up visits from 3 days to 12 months post-operatively, and the levels of angiopoietin-1 (Ang-1), vascular-endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), bone morphogenetic protein-2 (BMP-2), osteoprotegerin (OPG), tissue inhibitor of metalloproteinase 1 (TIMP-1), keratinocyte growth factor (KGF) and platelet-derived growth factor-AB (PDGF-AB) were measured. At baseline, 6 and 12 months post-surgery, periodontal clinical parameters were evaluated. ANOVA was applied to test for differences in the amount of mediators (p < 0.05).


Higher amounts of BMP-2 and OPG and a higher area under the curve (AUC) of KGF at the GTR versus AF sites were observed. The maximum change in the amount of KGF correlated significantly with periodontal clinical parameters at the GTR sites at 6 and 12 months. The AUC over 30 days of the amount of Ang-1, VEGF and KGF significantly correlated with periodontal clinical parameters at the AF sites at 6 months.


AF and GTR differentially affected the profile of the growth mediators in GCF, and significant correlations between certain GCF mediators and periodontal clinical outcomes were identified.

Clinical relevance

GCF components represent attractive prognostic markers for periodontal tissues undergoing repair or regeneration. However, the available evidence is not robust enough to suggest the use of a specific marker, and future adequately powered studies are warranted to identify the most relevant mediators that could be applied in clinical practice.


Gingival crevicular fluid Aggressive periodontitis Randomised controlled trial Periodontal surgery 



The study was supported by the Department of Periodontology, Eastman Dental Institute, London, UK.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the National Hospital for Neurology and Neuro-surgery/Institute of Neurology and the Eastman Joint Research Ethics Committee, London, UK (study reference: 04/Q0512/93). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • T. Rakmanee
    • 1
  • E. Calciolari
    • 2
  • I. Olsen
    • 3
  • U. Darbar
    • 4
  • G. S. Griffiths
    • 5
  • A. Petrie
    • 6
  • Nikolaos Donos
    • 2
  1. 1.Faculty of DentistryThammasat UniversityPathumthaniThailand
  2. 2.Centre for Oral Immunobiology and Regenerative Medicine & Centre for Oral Clinical Research, Institute of Dentistry, Barts and The London School of Medicine and DentistryQueen Mary University of London (QMUL)LondonUK
  3. 3.Division of Biomaterials and Tissue EngineeringUCL Eastman Dental InstituteLondonUK
  4. 4.Periodontology Unit, Department of Clinical ResearchUCL Eastman Dental HospitalLondonUK
  5. 5.School of Clinical DentistryUniversity of SheffieldSheffieldUK
  6. 6.Biostatistics UnitUCL Eastman Dental InstituteLondonUK

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