Groven Rald Victor Maria, Peniche Silva Carlos Julio, Balmayor Elizabeth Rosado, van der Horst Bart Nicolaas Jacobus, Poeze Martijn, Blokhuis Taco Johan, van Griensven Martijn
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands.
Division of Traumasurgery, Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.
J Orthop Translat. 2022 Aug 31;37:1-11. doi: 10.1016/j.jot.2022.07.002. eCollection 2022 Nov.
Immediately after a fracture occurs, a fracture hematoma (fxH) is formed. This fxH plays an important role in fracture healing and, under normal circumstances, aids in generating an environment in which a wide variety of cells orchestrate processes involved in fracture healing. MicroRNAs (miRNAs) may influence these processes. The aim of this study was therefore to determine the miRNA expression signature of human fxH in normal fracture healing and examine the potential influence of clinical parameters on these expression levels.
fxH was harvested from 61 patients ♀ during fracture surgery. miRNAs were isolated, transcribed and pooled for qPCR array analysis and validation. Qiagen fibrosis- and inflammation qPCR arrays were used based on an extensive literature study related to fracture healing and osteogenesis. Additionally, miRNA targets were determined.
From the array data, a selection of the twenty most regulated miRNAs, 10 up- and 10 down regulated, was validated in the study population. The expression levels of seven out of these twenty miRNAs were correlated to several clinical parameters. The time interval between trauma and surgery showed to influence the expression of three miRNAs, three other miRNAs were expressed in a patient age dependent manner and one miRNA was associated with the severity of trauma.
This study portrayed the role and importance of miRNAs in human fxH, linked to key processes in fracture healing. Seven miRNAs showed to be involved in multiple processes that are important in the fracture healing cascade, such as angiogenesis, mineralisation and cellular differentiation. target analysis revealed 260 mRNA targets for 14 out of the 20 validated miRNAs.
These data broaden our view on the potential diagnostic and therapeutic implications of miRNAs in fracture healing.
骨折发生后立即会形成骨折血肿（fxH）。这种fxH在骨折愈合中起重要作用，在正常情况下，有助于营造一个多种细胞协调参与骨折愈合过程的环境。微小RNA（miRNA）可能会影响这些过程。因此，本研究的目的是确定正常骨折愈合过程中人类fxH的miRNA表达特征，并研究临床参数对这些表达水平的潜在影响。
在骨折手术期间从61例女性患者中采集fxH。分离、转录miRNA并汇集用于qPCR阵列分析和验证。基于与骨折愈合和成骨相关的广泛文献研究，使用Qiagen纤维化和炎症qPCR阵列。此外，还确定了miRNA靶标。
从阵列数据中，在研究人群中验证了二十个调控最为显著的miRNA中的一部分，其中10个上调，10个下调。这二十个miRNA中的七个表达水平与几个临床参数相关。创伤与手术之间的时间间隔显示会影响三个miRNA的表达，另外三个miRNA以患者年龄依赖的方式表达，还有一个miRNA与创伤严重程度相关。
本研究描述了miRNA在人类fxH中的作用和重要性，与骨折愈合的关键过程相关。七个miRNA显示参与了骨折愈合级联反应中多个重要过程，如血管生成、矿化和细胞分化。靶标分析揭示了20个已验证miRNA中的14个的260个mRNA靶标。
这些数据拓宽了我们对miRNA在骨折愈合中的潜在诊断和治疗意义的认识。
