Rath-Deschner Birgit, Daratsianos Nikolaos, Dühr Sarah, Girmann Niklas, Winter Jochen, Kroll Franziska, Reichert Christoph, Jäger Andreas, Götz Werner
Department of Orthodontics, University of Bonn, Bonn, Germany.
J Orofac Orthop. 2010 Jan;71(1):17-31. doi: 10.1007/s00056-010-9929-7. Epub 2010 Feb 5.
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.
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.
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.
RUNX2是Runt基因家族中的一员，是骨骼系统发育过程中最重要的转录因子之一。近几十年来的研究表明，该因子在骨骼和软骨的发育、生长及成熟过程中发挥着主要作用。它在牙齿发育、机械转导和血管生成中也很重要，并且在各种病理过程（如肿瘤转移）中发挥着重要作用。RUNX2基因的突变与锁骨颅骨发育不全（CCD）综合征相关，该综合征对牙科，尤其是正畸学很重要，因为它具有牙齿和口腔颌面部症状。目前对实验诱导的小鼠突变体的研究使我们能够在细胞和分子生物学水平上研究这些畸形的病因和发病机制。本研究的目的是概述RUNX2基因的功能，特别是在骨骼发育方面，并总结我们迄今为止的研究工作，这些工作主要集中在研究RUNX2对下颌骨生长的影响，而在许多CCD患者中下颌骨生长仅有轻微改变或根本未改变。
进行免疫组织化学分析以揭示正常小鼠以及生长早期和晚期的杂合RUNX2基因敲除小鼠髁突软骨中的RUNX2；我们还进行了放射学和头影测量分析。
我们观察到RUNX2参与小鼠髁突的正常生长，并且可能在成骨和血管生成中发挥重要作用。RUNX2在软骨分区方面也存在生物力学相关性。在蛋白质水平上，我们注意到RUNX2在髁突中的出现和分布没有差异，除了出生后第4周和第6周的一个短暂阶段，因此一个等位基因可能足以实现基本正常的生长；其他生物因素可能具有补偿作用。然而，我们确实观察到杂合基因敲除动物下颌骨的一些头影测量参数有小的变化。我们通过将我们的发现与关于RUNX2生物学的最新知识相关联来讨论潜在的相关性。
