Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration

Fuxin Wei, Rui Zhong, Ximin Pan, Mohammed Khaleel, Aziz Hammoud, Zhiyu Zhou, Shaoyu Liu, Haixing Sun, Yajing Zhao, Xuenong Zou, Bo Jiang, Wenquan Zhuang, Ningning Chen, Yingming Chen

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalSpine Journal
DOIs
StateAccepted/In press - 2015

Fingerprint

Intervertebral Disc Degeneration
Tomography
Rabbits
Injections
Bone and Bones
Needles
Bone Marrow
Control Groups
Animal Models
Cartilage Oligomeric Matrix Protein
Magnetic Resonance Imaging
Disintegrins
Aggrecans
Matrix Metalloproteinase 3
Collagen Type II
von Willebrand Factor
Metalloproteases
bleomycetin
Radiography
Real-Time Polymerase Chain Reaction

Keywords

  • Animal model
  • Computed tomography
  • Degeneration
  • Intervertebral disc
  • Magnetic resonance imaging
  • Rabbits

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration. / Wei, Fuxin; Zhong, Rui; Pan, Ximin; Khaleel, Mohammed; Hammoud, Aziz; Zhou, Zhiyu; Liu, Shaoyu; Sun, Haixing; Zhao, Yajing; Zou, Xuenong; Jiang, Bo; Zhuang, Wenquan; Chen, Ningning; Chen, Yingming.

In: Spine Journal, 2015.

Research output: Contribution to journalArticle

Wei, Fuxin ; Zhong, Rui ; Pan, Ximin ; Khaleel, Mohammed ; Hammoud, Aziz ; Zhou, Zhiyu ; Liu, Shaoyu ; Sun, Haixing ; Zhao, Yajing ; Zou, Xuenong ; Jiang, Bo ; Zhuang, Wenquan ; Chen, Ningning ; Chen, Yingming. / Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration. In: Spine Journal. 2015.
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title = "Computed tomography-guided sub-end plate injection of pingyangmycin for a novel rabbit model of slowly progressive disc degeneration",
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.",
keywords = "Animal model, Computed tomography, Degeneration, Intervertebral disc, Magnetic resonance imaging, Rabbits",
author = "Fuxin Wei and Rui Zhong and Ximin Pan and Mohammed Khaleel and Aziz Hammoud and Zhiyu Zhou and Shaoyu Liu and Haixing Sun and Yajing Zhao and Xuenong Zou and Bo Jiang and Wenquan Zhuang and Ningning Chen and Yingming Chen",
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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

PY - 2015

Y1 - 2015

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

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