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The Significance of RUNX2 in Postnatal Development of the Mandibular Condyle

Die Bedeutung von RUNX2 in der postnatalen Entwicklung des Kondylus

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Abstract

Objective:

RUNX2, in the Runt gene family, is one of the most important transcription factors in the development of the skeletal system. Research in recent decades has shown that this factor plays a major role in the development, growth and maturation of bone and cartilage. It is also important in tooth development, mechanotransduction and angiogenesis, and plays a significant role in various pathological processes, i.e. tumor metastasization. Mutations in the RUNX2 gene correlate with the cleidocranial dysplasia (CCD) syndrome, important to dentistry, particularly orthodontics because of its dental and orofacial symptoms. Current research on experimentally-induced mouse mutants enables us to study the etiology and pathogenesis of these malformations at the cellular and molecular biological level. This study’s aim is to provide an overview of the RUNX2 gene’s function especially in skeletal development, and to summarize our research efforts to date, which has focused on investigating the influence of RUNX2 on mandibular growth, which is slightly or not at all altered in many CCD patients.

Materials and Methods:

Immunohistochemical analyses were conducted to reveal RUNX2 in the condylar cartilage of normal mice and of heterozygous RUNX2 knockout mice in early and late growth phases; we also performed radiographic and cephalometric analyses.

Results:

We observed that RUNX2 is involved in normal condylar growth in the mouse and probably plays a significant role in osteogenesis and angiogenesis. The RUNX2 also has a biomechanical correlation in relation to cartilage compartmentalization. At the protein level, we noted no differences in the occurrence and distribution of RUNX2 in the condyle, except for a short phase during the 4th and 6th postnatal weeks, so that one allele might suffice for largely normal growth; other biological factors may have compensatory effects. However, we did observe small changes in a few cephalometric parameters concerning the mandibles of heterozygous knockout animals. We discuss potential correlations to our findings by relating them to the most current knowledge about the RUNX2 biology.

Zusammenfassung

Ziel:

Zu den wichtigsten Transkriptionsfaktoren für die Entwicklung des Skelettsystems gehört RUNX2 aus der Familie der Runt- Gene. Die Forschungen der letzten Jahrzehnte zeigten, dass dieser Faktor eine große Rolle in der Entwicklung, dem Wachstum und der Reifung von Knochen und Knorpel spielt. Darüber hinaus ist er für Zahnentwicklung, Mechanotransduktion und Angiogenese wichtig und hat eine Bedeutung bei verschiedenen pathologischen Prozessen wie z.B. der Tumormetastasierung. Mutationen im RUNX2-Gen sind mit dem Syndrom der Dysplasia cleidocranialis (CCD) korreliert, das aufgrund seiner dentalen und orofazialen Symptomatik für die Zahnmedizin und insbesondere die Kieferorthopädie von Wichtigkeit ist. Die Untersuchung experimentell induzierter Mausmutanten erlaubt heutzutage Forschungen zur Ätiologie und Pathogenese dieser Fehlbildungen auf zell- und molekularbiologischer Ebene. Die vorliegende Arbeit soll eine Übersicht über die Funktion des RUNX2-Gens vor allem in der Skelettentwicklung und eine Zusammenfassung bisheriger eigener Forschungsarbeiten geben. Dabei ging es vor allem um die Frage des Einflusses von RUNX2 auf das Wachstum der Mandibula, die bei vielen CCD-Patienten nicht oder nur gering verändert ist.

Material und Methodik:

Immunhistochemische Untersuchungen wurden zum Nachweis von RUNX2 am Kondylenknorpel normaler Mäuse sowie von heterozygoten RUNX2-Knockout- Mäusen in frühen und späten Wachstumsphasen durchgeführt sowie röntgenologisch-kephalometrische Untersuchungen.

Ergebnisse:

RUNX2 war am normalen Kondylenwachstum der Maus beteiligt und wahrscheinlich auch in der Osteo- und Angiogenese sowie im Zusammenhang mit einer möglicherweise biomechanisch korrelierten Kompartimentierung des Knorpels von Bedeutung. Auf Proteinebene konnten bis auf eine kurze Phase während der 4. bis 6. postnatalen Woche keine Unterschiede im Auftreten und in der Verteilung von RUNX2 im Kondylus festgestellt werden, so dass womöglich ein Allel für ein weitgehend regelrechtes Wachstum ausreicht bzw. Kompensationen durch andere biologische Faktoren vermutet werden können. Dennoch konnten für einige kephalometrische Parameter an den Mandibulae heterozygoter Knockout-Tiere Veränderungen im Sinne einer reduzierten Dimension festgestellt werden. Mögliche Zusammenhänge zwischen diesen Befunden werden auf den Grundlagen neuer Erkenntnisse zur Biologie von RUNX2 diskutiert.

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Authors and Affiliations

  1. Department of Orthodontics, University of Bonn, Bonn, Germany

    Birgit Rath-Deschner, Nikolaos Daratsianos, Sarah Dühr, Niklas Girmann, Franziska Kroll, Christoph Reichert, Andreas Jäger & Werner Götz

  2. Department of Periodontology, Conservative and Preventive Dentistry, Molecular Biology Laboratory, University of Bonn, Bonn, Germany

    Jochen Winter

  3. Private Orthodontic Practice, Mainz, Germany

    Niklas Girmann

  4. Rheinische Friedrich-Wilhelms-Universität Bonn, Poliklinik für Kieferorthopädie, Welschnonnenstr. 17, 53111, Bonn, Germany

    Birgit Rath-Deschner

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  1. Birgit Rath-Deschner
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Rath-Deschner, B., Daratsianos, N., Dühr, S. et al. The Significance of RUNX2 in Postnatal Development of the Mandibular Condyle. J Orofac Orthop 71, 17–31 (2010). https://doi.org/10.1007/s00056-010-9929-7

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