Circulating miRNA signatures after trauma: The impact of trauma severity and nailing strategy

Introduction MicroRNAs (miRNAs) are key regulators of protein expression, and have shown several ties to tissue regeneration and fracture healing. Exact mechanisms by which miRNAs may elicit systemic effects after trauma are currently unclear.

Objectives To investigate the effect of trauma severity and utilized reaming technique for intramedullary nailing on the expression of circulating miRNAs in a porcine trauma model.

Materials & methods 36 pigs were randomized into two groups: monotrauma (MT; femur fracture only) and polytrauma (PT; femur fracture, and blunt chest trauma, liver laceration, and haemorrhagic shock). After a 60-minute shock phase, animals were operatively stabilized. Based on the applied reaming technique, three subgroups were composed: 1) SynReam, 2) RIA-1, and 3) RIA-2 (DePuy Synthes). Blood was collected at 1, 2, and 6 h after trauma. MiRNAs were isolated, transcribed and pooled for qPCR array analysis followed by in silico mRNA target prediction.

Results Compared to MT, the circulating miRNA-signature of PT at 1 h post-trauma had a more pro-inflammatory profile incl. deregulated miRNAs with ties to shock and/or tissue damage (miRNAs 93, 99a, and 107). At 2 h post-trauma, the pro-inflammatory character of the circulating miRNAs persisted while the expression of multiple anti-inflammatory miRNAs increased as well. Most deregulated miRNAs were observed at 6 h post-trauma, associated with the immune response and individual injuries of the trauma model itself. Ongoing research investigates potential differences in miRNA expression profiles between the different reamer subgroups.

Conclusion This study shows that miRNAs play a systemic role after trauma, and that trauma severity is associated with specific miRNA expression patterns over time. Interestingly, unique circulating miRNAs may reflect individual injuries in polytrauma, warranting further research into the potential application of miRNAs as diagnostic/prognostic markers after trauma.

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