The significance of RUNX2 in postnatal development of the mandibular condyle

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.