TY - JOUR
T1 - Computed tomography–guided sub–end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration
AU - Wei, Fuxin
AU - Zhong, Rui
AU - Pan, Ximin
AU - Khaleel, Mohammed
AU - Hammoud, Aziz
AU - Zhou, Zhiyu
AU - Liu, Shaoyu
AU - Sun, Haixing
AU - Zhao, Yajing
AU - Zou, Xuenong
AU - Jiang, Bo
AU - Zhuang, Wenquan
AU - Chen, Ningning
AU - Chen, Yingming
N1 - Funding Information:
This study was supported by National Natural Science Foundation of China ( 81401839 , 81272041 , and U1032001 ), National Basic Research Program of China (973 Program, 2012CB619105), China Postdoctoral Science Foundation ( 2013M531876 ), and Natural Science Foundation of Guangdong ( S2013010015775 ). The authors thank Shiqian Yu, Sannv Zheng, and Xuejun Dai for their technical and surgical assistance. The authors also thank Steffen Ringgaard for technical assistance of T1ρ imaging.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Animal model
KW - Computed tomography
KW - Degeneration
KW - Intervertebral disc
KW - Magnetic resonance imaging
KW - Rabbits
UR - http://www.scopus.com/inward/record.url?scp=85026780763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026780763&partnerID=8YFLogxK
U2 - 10.1016/j.spinee.2015.04.004
DO - 10.1016/j.spinee.2015.04.004
M3 - Article
C2 - 25862504
AN - SCOPUS:85026780763
SN - 1529-9430
VL - 19
SP - e6-e18
JO - Spine Journal
JF - Spine Journal
IS - 2
ER -