Fig. 6

SPOCK2 acts as an upstream molecule to regulate the MMP-2 activation in the development of NP. A Time course of changes in MMP-2 expression and activation in the spinal cord in the sham group at 1, 3, 7, 14, and 21 days after CCI operation. The sham operation group was used as control. B Pearson correlation analysis to examine the correlation between SPOCK2 and active-MMP-2 in the spinal cord after CCI (r > 0, p < 0.001). C Decreased expression level of SPOCK2 and active-MMP-2 after i.t. injection of SPOCK2-siRNA. (*P < 0.05 vs CCI + NC-siRNA). D Double staining showing decreased (**P < 0.01 vs CCI + NC-siRNA) colocalization of MMP-2 with GFAP after i.t. injection of SPOCK2-siRNA (Scale 50 μm). E Pearson correlation analysis to examine the correlation between SPOCK2 and active-MMP-2 in the spinal cord after i.t. injection of SPOCK2-siRNA in the rat CCI model (r > 0, p < 0.001). F Continuous i.t. injection of MMP-2 inhibitors for 7 days (from CCI 1 to 7 days) increased PWT and PWL at 3 and 7 days after CCI (*P < 0.05 vs CCI + DMSO [10%]). G Decreased expression and activation of MMP-2 after i.t. injection of MMP-2 inhibitors. (*P < 0.05 vs CCI + DMSO [10%]). The change in expression of SPOCK2 was not significant (P > 0.05 vs CCI + DMSO [10%]) after i.t. injection of MMP-2 inhibitors. H Increased expression of SPOCK2 and active-MMP-2 after i.t. injection of rSPOCK2 in SD rats. (*P < 0.05 vs Vehicle). Decreased expression of active-MMP-2 after i.t injection of rSPOCK2 followed by i.t. injection of MMP-2 inhibitors (*P < 0.05 vs rSPOCK2), but the change in expression of SPOCK2 was not significant (P > 0.05 vs rSPOCK2). I i.t. injection of rSPOCK2 (0.3 ng, twice daily) in SD rats decreased PWT and PWL at 16 h (Day 4) after the end of injection (*P < 0.05 vs Vehicle). In addition, PWT and PWL showed relatively increased in the rSPOCK2 + MMP-2 inhibitor group (#P < 0.05 vs rSPOCK2)