Molecular biology of periodontal ligament fibroblasts and orthodontic tooth movement

Evidence and possible role of the circadian rhythm
  • David Andreas HilbertEmail author
  • Svenja Memmert
  • Jana Marciniak
  • Andreas Jäger
Original Article



The circadian clock plays an important role in many physiological states and pathologies. The significance of its core genes in bone formation and tooth development has already been demonstrated. However, regulation of these genes and their influence on periodontal and bone remodeling in periodontal ligament (PDL) fibroblasts remains to be elucidated. Our hypothesis was that the circadian clock influences markers for periodontal and bone remodeling and therefore orthodontic tooth movement itself.

Materials and methods

Human PDL fibroblasts were cultured and synchronized in circadian rhythms with the help of a dexamethasone shock. Cells were harvested at 4 h intervals. Reverse transcription and quantitative RT PCR (real time polymerase chain reaction) were performed to assess the mRNA levels of the clock genes ARNTL, CLOCK1, PER1, and PER2. Subsequently, mRNA expression of important marker genes for periodontal and bone remodeling, OPG, RANKL, OCN, OPN, RUNX2, COL1A1, IL1β, KI67, and POSTN, were examined at time points of ARNTL amplitude expression.


Gene expression of core clock genes varied over 48 h in accordance with the circadian rhythm. Functional markers, except KI67, showed significant differences at time points of maximum fluctuation especially of ARNTL.


PDL fibroblasts express circadian clock genes. Our results suggest that genes associated with bone and periodontal remodeling are influenced by the circadian rhythm. Further research will have to refine the understanding of this influence for orthodontic treatment.


Chronobiology Circadian rhythm signaling peptides and proteins Orthodontics Tooth movement ARNTL transcription factors 

Molekularbiologie von parodontalen Ligamentfibroblasten und kieferorthopädische Zahnbewegung

Evidenz und mögliche Bedeutung der zirkadianen Rhythmik



Die zirkadiane Rhythmik spielt eine wichtige Rolle im Rahmen sowohl physiologischer als auch pathologischer Prozesse. Eine Bedeutung der Core-Clock-Gene für die Knochenbildung und die Zahnentwicklung konnte bereits dargestellt werden. Eine Regulation dieser Gene und ihr Einfluss auf das parodontale und ossäre Remodeling durch PDL(paradontale Ligament)-Fibroblasten wurde jedoch noch nicht näher untersucht. Unsere Hypothese war, dass die zirkadiane Uhr wichtige Faktoren des parodontalen wie des ossären Remodeling beeinflusst und damit auch die kieferorthopädische Zahnbewegung selbst.

Material und Methoden

Humane PDL-Fibroblasten wurden kultiviert und mithilfe eines Dexamethasonschocks in ihren zirkadianen Rhythmen synchronisiert. Die Zellen wurden in 4‑Stunden-Intervallen geerntet. Reverse Transkription und quantitative RT-PCR („real time polymerase chain reaction“) wurden durchgeführt, um die Genexpression der Core-Clock-Gene ARNTL, CLOCK1, PER1 und PER2 zu bestimmen. Anschließend wurde die Genexpression wichtiger Marker für das parodontale und ossäre Remodeling wie OPG, RANKL, OCN, OPN, RUNX2, COL1A1, IL1β, KI67, POSTN zu Zeitpunkten der maximalen bzw. minimalen Expression der ARNTL-Genexpression untersucht.


Die Genexpression von Core-Clock-Genen variierte über 48 h entsprechend dem zirkadianen Rhythmus. Alle funktionellen Marker, bis auf KI67, zeigten signifikante Unterschiede zu Zeitpunkten der maximalen bzw. minimalen Expression von ARNTL.


PDL-Fibroblasten exprimieren Gene der zirkadianen Uhr. Unsere Ergebnisse deuten darauf hin, dass Gene, die mit ossärem und parodontalem Remodeling assoziiert sind, durch die zirkadiane Rhythmik beeinflusst werden. Weitere Forschungen werden das Verständnis dieses Einflusses auf die kieferorthopädische Behandlung vertiefen müssen.


Chronobiologie Zirkadiane Rhythmik, Signalpeptide und -proteine Kieferorthopädie Zahnbewegung ARNTL-Transkriptionsfaktor 



The authors would like to thank Prof. Helmut Stark, Ms. Silke van Dyck and Ms. Inka Bay for their valuable support.

Conflict of interest

D.A. Hilbert, S. Memmert, J. Marciniak and A. Jäger declare that they have no competing interests.


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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • David Andreas Hilbert
    • 1
    Email author
  • Svenja Memmert
    • 2
    • 3
  • Jana Marciniak
    • 2
  • Andreas Jäger
    • 2
  1. 1.Department of Prosthodontics, Preclinical Education and Dental Materials ScienceUniversity of BonnBonnGermany
  2. 2.Department of Orthodontics, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany
  3. 3.Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany

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