The Role of Periodontal Ligament Cells in Delayed Tooth Eruption in Patients with Cleidocranial Dysostosis*

  • Stefan Lossdörfer
  • Bassel Abou Jamra
  • Birgit Rath-Deschner
  • Werner Götz
  • Rami Abou Jamra
  • Bert Braumann
  • Andreas Jäger
Original Article
First Online:
Received:
Accepted:

Abstract

Objective:

The clinical appearance of patients with cleidocranial dysplasia (CCD), which is caused by mutations in the RUNX2 gene, is characterized by anomalies of the clavicles, thorax, spine, pelvis and extremities and by disturbances of the skull and tooth development. Of orthodontic relevance are multiple supernumerary teeth associated with delayed tooth eruption. The present investigation is based on the hypothesis that an altered phenotypic expression of periodontal ligament (PDL) cells from CCD patients and a reduced ability of those cells to support the differentiation of bone-resorbing osteoclasts might contribute to delayed tooth eruption.

Materials and Methods:

To test this hypothesis, PDL cells from healthy donors and from two patients with clinically and molecular biologically diagnosed CCD were characterized for the basal and induced mRNA expression of osteoblast marker genes. The physiological relevance of the findings for the differentiation of osteoclasts was examined in an osteoclast assay, as well as in a co-culture model of PDL cells and osteoclast precursors.

Results:

Both CCD patients displayed missense mutations of the RUNX2 gene. The in vitro experiments revealed an unaltered expression of RUNX2 mRNA, however especially in CCD patient 2 there was a reduced basal expression of mRNA for the key regulatory gene for bone remodeling RANKL. Furthermore, compared to the control cells from healthy donors, these factors were less inducible by stimulation of the cultures with 1α,25(OH)2D3. In the osteoclast assays as well as in the co-culture experiments, PDL cells from the CCD patients showed a reduced capacity to induce the differentiation of active osteoclasts.

Conclusions:

These data indicate that PDL cells from CCD patients express a less distinctive osteoblastic phenotype resulting in an impaired ability to support osteoclastogenesis which might, in part, account for the delayed tooth eruption that can be observed clinically.

Key Words:

Cleidocranial dysplasia Tooth eruption Human PDL cells Osteoclastogenesis OPG RANKL In vitro 

Die Rolle der Parodontalligamentzellen im Rahmen des gestörten Zahndurchbruchs bei Patienten mit Cleidocranialer Dysostose*

Zusammenfassung

Zielsetzung:

Das klinische Bild der Cleidocranialen Dysplasie (CCD), das durch Mutationen im Bereich des Transkriptionsfaktors RUNX2 verursacht wird, ist durch Schlüsselbeinanomalien, Störungen der Schädel- bzw. Zahnentwicklung sowie Veränderungen im Bereich von Thorax, Wirbelsäule, Becken und Extremitäten geprägt. Besonders auffällig und von kieferorthopädischer Relevanz sind multiple überzählige Zähne sowie ein verzögerter Zahndurchbruch. Der vorliegenden Untersuchung liegt die Hypothese zugrunde, dass eine veränderte phänotypische Expression der Zellen der Parodontalligaments (PDL) von CCD-Patienten und daraus resultierend eine eingeschränkte Fähigkeit zur Unterstützung der Aktivität von knochenresorbierenden Osteoklasten für diesen erschwerten Zahndurchbruch mitverantwortlich sein könnten.

Material und Methodik:

Zur Überprüfung dieser Annahme wurden PDL-Zellen von gesunden Spendern und solchen mit klinisch und molekularbiologisch diagnostizierter CCD bezüglich des Auftretens und der Induzierbarkeit osteoblastärer Markergene auf mRNA-Ebene charakterisiert und die physiologische Relevanz dieser Befunde für die Differenzierung von Osteoklasten aus entsprechenden Vorläuferzellen in einem Osteoklastenassay sowie in einem Kokulturmodell vergleichend näher untersucht.

Ergebnisse:

Dabei konnte zunächst bei beiden CCD-Patienten eine Missense-Mutation im Bereich des RUNX2-Gens nachgewiesen werden. In den In-vitro-Versuchen zeigte sich für die PDLZellen eine unveränderte Expression von RUNX2 mRNA, jedoch insbesondere bei CCD-Patient 2 eine reduzierte basale Expression der mRNA für das osteoklastenregulatorische Molekül RANKL. Außerdem ließen sich diese Faktoren im Vergleich zur Kontrollgruppe der gesunden Donoren nur vermindert durch Stimulation der Kulturen mit 1α,25(OH)2D3 induzieren. In den durchgeführten Osteo klastenassays sowie in den Kokulturversuchen zeigten die PDL-Zellen der CCD-Patienten eine verringerte Potenz zur Induktion von aktiven Osteoklasten.

Schlussfolgerungen:

Die erhobenen Daten implizieren einen geringer gradig ausgeprägten osteoblastären Phänotyp der PDLZellen bei den untersuchten CCD-Patienten mit einer resultierenden eingeschränkten Fähigkeit zur Unterstützung der Osteoklastogenese, die letztlich für den klinisch zu beobachtenden erschwerten Zahndurchbruch mitverantwortlich sein könnte.

Schlüsselwörter:

Cleidocraniale Dysplasie Zahndurchbruch humane PDL-Zellen Osteoklastogenese OPG RANKL In vitro 
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Copyright information

© Urban & Vogel, Muenchen 2009

Authors and Affiliations

  • Stefan Lossdörfer
    • 1
    • 5
  • Bassel Abou Jamra
    • 2
  • Birgit Rath-Deschner
    • 1
  • Werner Götz
    • 1
  • Rami Abou Jamra
    • 3
  • Bert Braumann
    • 4
  • Andreas Jäger
    • 1
  1. 1.Department of OrthodonticsUniversity of BonnBonnGermany
  2. 2.Department of OrthodonticsUniversity of RostockRostockGermany
  3. 3.Institute of Human GeneticsUniversity of BonnBonnGermany
  4. 4.Department of OrthodonticsUniversity of CologneCologneGermany
  5. 5.Poliklinik für KieferorthopädieRheinische Friedrich-Wilhelms-UniversitätBonnGermany

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