An in vivo model of reduced nucleus pulposus glycosaminoglycan content in the rat lumbar intervertebral disc.
METHODS
An in vivo model resembling early stage disc degeneration in the rat lumbar spine.


OBJECTIVE
Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC).


BACKGROUND
Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention.


METHODS
ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection.


RESULTS
At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan.


CONCLUSIONS
An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration.
Boxberger
John I
JI
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19104-6081, USA.
Auerbach
Joshua D
JD
Sen
Sounok
S
Elliott
Dawn M
DM
D000818:Animals; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D004195:Disease Models, Animal; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D008297:Male; D016059:Range of Motion, Articular; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D014057:Tomography, X-Ray Computed
D019765:Chondroitin ABC Lyase