Pingyangmycin-induced in vivo lumbar disc degeneration model of rhesus monkeys.

Abstract

Animal experimental study. To establish a slowly progressive and reproducible intervertebral disc degeneration model and determine the performance of T1ρ magnetic resonance imaging in the evaluation of disc degeneration. Recently, one of the hotspots of research efforts was related to management of early stage of disc degeneration. To our knowledge, a functional animal model that mimics ischemic and slowly progressive disc degeneration of humans does not exist. The subchondral bone adjacent to the lumbar intervertebral discs (from L3-L4 to L6-L7) of 8 rhesus monkeys was randomly injected with 4 mL of Pingyangmycin (PYM) solution (1.5 mg/mL, PYM), or 4 mL of phosphate buffered saline (Vehicle control), or exteriorized but not injected anything (Sham), respectively. The degenerative process was investigated by using radiography and T1ρ magnetic resonance imaging at 1, 3, 6, 9, 12, and 15 months postoperatively. Histological scoring, immunohistochemistry, and real-time polymerase chain reaction were performed at 15 months. The mean T1ρ values of nucleus pulposus and annulus fibrosus in the PYM group significantly decreased after 3 and 6 months, respectively, followed by slow decrease, and the histological score was significantly higher at 15 months, compared with the control groups. The results of molecular analysis revealed a significant increase matrix metalloprotease-3, A disintegrin and metalloproteinase with thrombospondin motifs -5, tumor necrosis factor α, interleukin-1β, interleukin-6 expressions, and marked reduction in aggrecan, type II collagen, von Willebrand factor expressions at the messenger RNA levels in the PYM group. Spearman correlation analysis of Pfirrmann grades showed significantly inverse correlation with T1ρ values of nucleus pulposus and annulus fibrosus (r = -0.634, -0.617, respectively, P < 0.01). Injection of PYM into the subchondral bone adjacent to the lumbar intervertebral discs of rhesus monkeys can results in mild, slowly progressive disc degeneration, which mimics the onset of human disc degeneration, and the T1ρ magnetic resonance imaging is suited for evaluating intervertebral disc degeneration. N/A.