SPP1 expression after spinal cord compression injury and its effects on glial cell activation

To study the role and mechanism of SPP1 in spinal cord injury.

We created a rat model of spinal cord compression injury (SCI) and examined the expression of SPP1 in spinal cord tissue using western blotting and immunofluorescence staining. We assessed motor function and pathological repair in SCI rats using the BBB locomotor scale, swimming tests, HE staining, Nissl staining, myelin staining, immunofluorescence, and western blot experiments. Additionally, we examined microglial activation and inflammatory phenotypes to analyze underlying mechanisms. To determine if SPP1's effects are linked to MK2, we used the MK2 inhibitor PF-364402.

After spinal cord injury, the expression level of SPP1 exhibited a significant increase, peaking on the third day post-injury. A co-localization relationship was noted with Iba-1-labeled microglia. Reduced SPP1 expression enhanced motor function recovery and aided in spinal cord tissue repair after injury in mice. Low SPP1 expression modulated glial cell inflammation, reducing the iNOS-labeled pro-inflammatory phenotype and increasing the Arg-1-labeled anti-inflammatory phenotype. This modulation subsequently inhibited the activation of microglia. Furthermore, we validated the inhibitory effect of low SPP1 expression on the activation of the MK2 signaling pathway, which was associated with a reduction in the phosphorylation levels of MK2, p38, and NF-κB.

This study found that SPP1 was highly expressed in rats with spinal cord injury and was associated with microglial activation and inflammatory phenotype transformation. Low levels of SPP1 promoted neural repair and motor function recovery, which may be related to the MK2 pathway.