Effect of the adenovirus‑mediated Wip1 gene on lumbar intervertebral disc degeneration in a rabbit model

Abstract

The present study aimed to investigate the effect of the adenovirus‑mediated wild‑type p53‑induced protein phosphatase 1 (Wip1) gene on lumbar disc degeneration (LDD) in a rabbit model. Adult New Zealand white rabbits were used as experimental subjects. The rabbits were divided into LDD groups (groups A‑C of rabbit models of LDD) and control groups (groups D‑F of normal rabbits). The animals in groups A and D were injected with the Wip1 gene vector, those in groups B and E were injected with an empty vector, and those in groups C and F were injected with phosphate‑buffered saline. Type II collagen was detected using a streptavidin‑biotin complex immunohistochemistry method. Postoperative X‑ray imaging showed a significant increase in the recovery of rabbits from group A, compared with those from groups B and C. The nucleus pulposus proteoglycan content of the intervertebral discs (L2‑3, L3‑4 and L4‑5) of group A remained higher, compared with the content in groups B and C, and the values in groups B and C differed from those of groups E and F. At 3, 6 and 9 weeks post‑injection, the content of type II collagen of intervertebral discs (L2‑3, L3‑4 and L4‑5) in group A differed from groups B and C, and the values in groups A‑C remained lower, compared with those in groups D‑F. The Wip1 gene exhibited a therapeutic effect in the treatment of LDD.

Figure 1.

Transfection of nucleus pulposus cells by AdWip1 at different viral concentrations. Images were captured under a fluorescence microscope (magnification, ×100). (A) 25 MOI; (B) 50 MOI; (C) 100 MOI; (D) 200 MOI; (E) 400 MOI; (F) 800 MOI. Ad, adenovirus; Wip1, wild-type p53-induced protein phosphatase 1; MOI, multiplicity of infection.

Figure 2.

Numbers of nucleus pulposus cells. (A) Virus infection group and (B) blank control group (magnification, ×100). (C) Growth curve of nucleus pulposus cells in the virus infection group (200 MOI) and blank control group (0 MOI). MOI, multiplicity of infection.

Figure 3.

At different time points following AdWip1 transfection, the nucleus pulposus tissues of the intervertebral disc were made into slides and observed under a fluorescence microscope (magnification, ×200), (A) 7 days post-transfection; (B) 14 days post-transfection; (C) 21 days post-transfection; (D) 28 days post-transfection. Ad, adenovirus; Wip1, wild-type p53-induced protein phosphatase 1.

Figure 4.

X-ray results of intervertebral space degeneration in the model group. The images present (A) a narrowing of the intervertebral space, (B) osteophyte formation and (C) alterations in the cartilage endplate. Red arrows indicate the intervertebral space following the establishment of the model.