Department of Medicine, University of Verona, 37100 Verona, Italy.
Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37100 Verona, Italy.
Int J Mol Sci. 2021 Sep 25;22(19):10336. doi: 10.3390/ijms221910336.
Cleidocranial dysplasia (CCD), a dominantly inherited skeletal disease, is characterized by a variable phenotype ranging from dental alterations to severe skeletal defects. Either de novo or inherited mutations in the gene have been identified in most CCD patients. Transcription factor , the osteogenic master gene, plays a central role in the commitment of mesenchymal stem cells to osteoblast lineage. With the aim to analyse the effects of mutations in CCD patients, we investigated gene expression and the osteogenic potential of two CCD patients' cells. In addition, with the aim to better understand how mutations interfere with osteogenic differentiation, we performed string analyses to identify proteins interacting with RUNX2 and analysed p53 expression levels. Our findings demonstrated for the first time that, in addition to the alteration of downstream gene expression, mutations impair p53 expression affecting osteogenic maturation. In conclusion, the present work provides new insights into the role of mutations in CCD patients and suggests that an in-depth analysis of the -associated gene network may contribute to better understand the complex molecular and phenotypic alterations in mutant subjects.
颅锁骨发育不全（CCD）是一种显性遗传的骨骼疾病，其特征是表型多变，从牙齿改变到严重的骨骼缺陷。大多数 CCD 患者的基因中均发现了从头或遗传突变。转录因子，成骨主基因，在间充质干细胞向成骨细胞谱系的分化中起核心作用。为了分析 CCD 患者基因突变的影响，我们研究了两位 CCD 患者细胞的基因表达和成骨潜能。此外，为了更好地了解突变如何干扰成骨分化，我们进行了串扰分析以鉴定与 RUNX2 相互作用的蛋白质，并分析了 p53 表达水平。我们的研究结果首次表明，除了下游基因表达的改变外，突变还会影响 p53 的表达，从而影响成骨成熟。总之，本研究工作为 CCD 患者中突变的作用提供了新的见解，并表明对 - 相关基因网络的深入分析可能有助于更好地理解突变患者中复杂的分子和表型改变。
