Developing consistently reproducible intervertebral disc degeneration at rat caudal spine by using needle puncture.
OBJECTIVE
The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration.


METHODS
Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery.


RESULTS
The 18- and 21-gauge needle-stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP-anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O- and collagen type II-stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration.


CONCLUSIONS
After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.
Zhang
Huina
H
Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
La Marca
Frank
F
Hollister
Scott J
SJ
Goldstein
Steven A
SA
Lin
Chia-Ying
CY
D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D007403:Intervertebral Disc / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009339:Needles; D016602:Needlestick Injuries / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013623:Tail
D024043:Collagen Type II; C498220:Bmpr2 protein, rat; D052006:Bone Morphogenetic Protein Receptors, Type II