RNA Interference for the Prophylaxis of Combat Trauma-Induced Heterotopic Ossification.

摘要

Heterotopic ossification encompasses any pathology in which there is bone formation outside the skeleton. This condition can be induced by combat polytrauma, neurological injury, and hip arthroplasties. The clinical effects include joint anklyosis, pressure ulcers, and hindering rehabilitation. While current modalities have moderate successes in preventing HO, they do not specifically target osteogenesis. As a result, these therapies are often associated with undesirable side effects, as well as the recurrence of HO. Herein, we discuss and investigate the advantages of harnessing RNA interference to specifically knock down key osteogenic markers, thereby inhibiting osteoblast lineage progression. Furthermore, we analyzed the biocompatibility and transfection efficacy of nanostructured polymers as siRNA intracellular delivery vehicles in the mammalian pre-osteoblast cell line MC3T3-E1.4. We discovered that these polymers were biocompatible at the dosages tested, could complex with siRNA, and demonstrated significant gene and protein knockdown.