Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury.

STUDY DESIGN:Basic science study using a hemi-section spinal cord injury (SCI) model. OBJECTIVE:We sought to assess the effect of blocking Osteopontin (OPN) up-regulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. SUMMARY OF BACKGROUND DATA:OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. METHODS:We constructed a SCI mouse model and analyzed the expression of OPN at different time points, and the particular cell distribution in the injured spinal cord. Then, we blocked OPN up-regulation with lentivirus delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. RESULTS:The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was increased significantly 3 weeks after SCI. Suppressing the OPN up-regulation via siRNA exacerbated motor function impairment and neuropathic pain. Additionally, SCI resulted in an increase in the vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. CONCLUSION:OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the pro-angiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways.