Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat.
METHODS
In 2 studies, the injection of chondroitinase ABC into intervertebral discs of mature goats was evaluated as an experimental disc degeneration model. The first study analyzed the development of degeneration in time; the second study determined the optimal enzyme concentration.


OBJECTIVE
To develop reproducible, slowly progressive disc degeneration in a large animal model.


BACKGROUND
Currently available, small animal models of intervertebral disc degeneration have shortcomings in the comparability to humans in terms of size, geometry, and cell population. Also, the methods to induce degeneration in the current models do not mimic human degeneration, which starts with the loss of proteoglycans. Injecting the enzyme chondroitinase ABC into the nucleus pulposus mimics the loss of proteoglycans.


METHODS
In Study 1, lumbar intervertebral discs of 17 goats were injected with chondroitinase ABC (0.25 U/mL) or phosphate-buffered saline. Degeneration was analyzed with radiograph analysis, MR imaging, and macroscopic and histologic scoring at 5 different time points (4, 8, 12, 18, and 26 weeks). Six control goats were analyzed. The second study used 6 goats in which 4 different concentrations of chondroitinase ABC (0.2-0.35 U/mL) or phosphate-buffered saline were injected. After 12 weeks, similar analyses as in Study 1 were performed.


RESULTS
After 12 weeks, degenerative signs were observed in all parameters in Study 1. The degeneration increased up to 18 weeks and leveled off after 26 weeks. The variability, however, was high. The second study showed a concentration dependent effect of chondroitinase ABC with all analyzed parameters. The injection of 0.25 U/mL chondroitinase ABC resulted in disc degeneration after 12 weeks without signs of severe degeneration.


CONCLUSIONS
Injection of chondroitinase ABC in the caprine intervertebral disc results in mild, slowly progressive disc degeneration. This effect was optimal at a concentration of 0.25 U/mL. This is a promising model of disc degeneration that deserves further study.
Hoogendoorn
Roel J
RJ
Department of Orthopaedic Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Wuisman
Paul I
PI
Smit
Theo H
TH
Everts
Vincent E
VE
Helder
Marco N
MN
D000818:Animals; D019765:Chondroitin ABC Lyase; D004195:Disease Models, Animal; D018450:Disease Progression; D006041:Goats; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D008159:Lumbar Vertebrae; D008279:Magnetic Resonance Imaging; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013122:Spinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D011509:Proteoglycans; D019765:Chondroitin ABC Lyase