Fuxin Wei1, Rui Zhong1, Ximin Pan2, Mohammed Khaleel3, Aziz Hammoud4, Zhiyu Zhou1, Shaoyu Liu5, Haixing Sun2, Yajing Zhao6, Xuenong Zou1, Bo Jiang2, Wenquan Zhuang7, Ningning Chen1, Yingming Chen2. 1. Department of Spine Surgery, The First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, No. 58 Zhongshan Er Rd, Guangzhou 510080, People's Republic of China. 2. Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Er Rd, Guangzhou 510080, People's Republic of China. 3. Department of Orthopaedic Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. 4. The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. 5. Department of Spine Surgery, The First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, No. 58 Zhongshan Er Rd, Guangzhou 510080, People's Republic of China. Electronic address: gzsyliu@tom.com. 6. The Medical College of Sun Yat-sen University, No. 74 Zhongshan Er Rd, Guangzhou 510080, People's Republic of China. 7. Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Er Rd, Guangzhou 510080, People's Republic of China.
Abstract
BACKGROUND CONTEXT: Different animal models are used in disc degenerative disease 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: This is an experimental animal study of disc degeneration. PURPOSE: The purpose of this study was to establish an ischemic and slowly progressive intervertebral disc (IVD) degeneration model with an injection of pingyangmycin (PYM) into subchondral bone adjacent to the disc, using bone marrow needle guided by computed tomography (CT) scan. METHODS: The subchondral bone adjacent to the lumbar IVDs (from L3-L4 to L5-L6) of 18 rabbits was randomly injected with 3 mL PYM solution (1.5 mg/mL PYM), 3 mL phosphate-buffered saline (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 at 1, 3, and 6 months postoperatively, combined with histological scoring, immunohistochemistry, and real-time polymerase chain reaction 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<.05). The magnetic resonance imaging 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 months to the end point (p<.05). The bone tissue area of the end plate increased significantly at the end point, compared with that of the control groups (p<.05). The results of molecular analysis showed significant increase of matrix metalloproteinase-3, a disintegrin and metalloproteinase with thrombospondin motif-5, and marked reduction of aggrecan and Type II collagen after 3 months at the messenger RNA levels in the discs of PYM group (p<.05). The von Willebrand factor expression of PYM group also showed a significant reduction after 1 month (p<.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 result in ischemic and slowly progressive disc degeneration model, which mimics the onset of human disc degeneration.
BACKGROUND CONTEXT: Different animal models are used in disc degenerative disease 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: This is an experimental animal study of disc degeneration. PURPOSE: The purpose of this study was to establish an ischemic and slowly progressive intervertebral disc (IVD) degeneration model with an injection of pingyangmycin (PYM) into subchondral bone adjacent to the disc, using bone marrow needle guided by computed tomography (CT) scan. METHODS: The subchondral bone adjacent to the lumbar IVDs (from L3-L4 to L5-L6) of 18 rabbits was randomly injected with 3 mL PYM solution (1.5 mg/mL PYM), 3 mL phosphate-buffered saline (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 at 1, 3, and 6 months postoperatively, combined with histological scoring, immunohistochemistry, and real-time polymerase chain reaction 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<.05). The magnetic resonance imaging 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 months to the end point (p<.05). The bone tissue area of the end plate increased significantly at the end point, compared with that of the control groups (p<.05). The results of molecular analysis showed significant increase of matrix metalloproteinase-3, a disintegrin and metalloproteinase with thrombospondin motif-5, and marked reduction of aggrecan and Type II collagen after 3 months at the messenger RNA levels in the discs of PYM group (p<.05). The von Willebrand factor expression of PYM group also showed a significant reduction after 1 month (p<.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 result in ischemic and slowly progressive disc degeneration model, which mimics the onset of humandisc degeneration.