Computed Tomography Guided Subendplate Injection of Pingyangmycin for A Novel Rabbit Model of Slowly Progressive Disc Degeneration

Abstract Background Different animal models are used in disc degenerative disease(DDD) research by now. To our knowledge, a functional animal model that mimics ischemic and slowly progressive disc degeneration of humans does not exist. Study Design An experimental animal study of disc degeneration. Purpose To establish an ischemic and slowly progressive intervertebral disc (IVD) degeneration model with injection of Pingyangmycin into subchondral bone adjacent to the disc, using bone marrow needle guided by CT scan. Methods The subchondral bone adjacent to the lumbar IVDs (from L3/4 to L5/6) of eighteen rabbits was randomly injected with 3 ml Pingyangmycin (PYM) solution (1.5mg/ml, PYM), 3 ml PBS (Vehicle control), or exteriorized but not injected with anything (Sham), with using bone marrow needle guided by CT scan. The degenerative process was investigated by using radiography and magnetic resonance imaging (MRI) at 1, 3, and 6 months postoperatively, combined with histological scoring, immunohistochemistry and real-time PCR analysis. Results Significant disc space narrowing was observed at 6 months in the discs adjacent to the subchondral bone injected with PYM, compared with the control groups(P＜0.05). The MRI assessment also demonstrated a progressive loss of T2-weighted signal intensity postoperatively. The histological score increased significantly compared with that of the control groups from 3-month to the end point (P＜0.05). The bone tissue area of the endplate increased significantly at the end point, compared with that of control groups(P＜0.05). The results of molecular analysis showed significant increase of matrix metalloprotease(MMP)-3, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and marked reduction of aggrecan and type II collagen after 3 months at the mRNA levels in the discs of PYM group (P＜0.05). The von willebrand factor (vWF) expression of PYM group also showed a significant reduction after 1 month(P＜0.05). Conclusions Percutaneous injection of PYM into the subchondral bone adjacent to the lumbar IVDs of rabbits, using bone marrow needle guided by CT scan, can results in ischemic and slowly progressive disc degeneration model, which mimics the onset of human disc degeneration.