Botor Malwina, Auguściak-Duma Aleksandra, Lesiak Marta, Sieroń Łukasz, Dziedzic-Kowalska Agata, Witecka Joanna, Asman Marek, Madetko-Talowska Anna, Bik-Multanowski Mirosław, Galicka Anna, Sieroń Aleksander L, Gawron Katarzyna
Department of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland.
Department of Parasitology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland.
Pharmaceuticals (Basel). 2023 Oct 4;16(10):1414. doi: 10.3390/ph16101414.
() is a group of connective tissue disorders leading to abnormal bone formation, mainly due to mutations in genes encoding collagen type I (Col I). Osteogenesis is regulated by a number of molecules, including microRNAs (miRNAs), indicating their potential as targets for therapy. The goal of this study was to identify and analyze the expression profiles of miRNAs involved in bone extracellular matrix (ECM) regulation in patients diagnosed with type I caused by mutations in or . Primary skin fibroblast cultures were used for DNA purification and sequence analysis, followed by analysis of miRNA expression. Sequencing analysis revealed mutations of the or genes in all patients, including four previously unreported. Amongst the 40 miRNAs analyzed, 9 were identified exclusively in cells and 26 in both patients and the controls. In the latter case, the expression of six miRNAs (hsa-miR-10b-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, has-miR-204-5p, has-miR-216a-5p, and hsa-miR-449a) increased, while four (hsa-miR-129-5p, hsa-miR-199b-5p, hsa-miR-664a-5p, and hsa-miR-30a-5p) decreased significantly in cells in comparison to their expression in the control cells. The identified mutations and miRNA expression profiles shed light on the intricate processes governing bone formation and ECM regulation, paving the way for further research and potential therapeutic advancements in and other genetic diseases related to bone abnormality management.
（）是一组导致骨形成异常的结缔组织疾病，主要是由于编码I型胶原蛋白（Col I）的基因突变所致。骨生成受多种分子调控，包括微小RNA（miRNA），这表明它们具有作为治疗靶点的潜力。本研究的目的是鉴定和分析在因或突变而诊断为I型的患者中参与骨细胞外基质（ECM）调节的miRNA的表达谱。原代表皮成纤维细胞培养物用于DNA纯化和序列分析，随后进行miRNA表达分析。测序分析揭示了所有患者中的或基因的突变，包括四个先前未报道的突变。在分析的40种miRNA中，9种仅在细胞中鉴定到，26种在患者和对照中均有鉴定到。在后一种情况下，六种miRNA（hsa-miR-10b-5p、hsa-miR-19a-3p、hsa-miR-19b-3p、has-miR-204-5p、has-miR-216a-5p和hsa-miR-449a）的表达增加，而四种（hsa-miR-129-5p、hsa-miR-199b-5p、hsa-miR-664a-5p和hsa-miR-30a-5p）在细胞中的表达与对照细胞相比显著降低。所鉴定的突变和miRNA表达谱揭示了控制骨形成和ECM调节的复杂过程，为和其他与骨异常管理相关的遗传疾病的进一步研究和潜在治疗进展铺平了道路。
