Human intervertebral disc aggrecan inhibits nerve growth in vitro.
OBJECTIVE
To assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques.


METHODS
Aggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH-SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared.


RESULTS
Disc aggrecan inhibited the growth of neurites from SH-SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration-dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects.


CONCLUSIONS
Nerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.
Johnson
William E B
WE
Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK. w.e.b.Johnson@keele.ac.uk
Caterson
Bruce
B
Eisenstein
Stephen M
SM
Hynds
Dianna L
DL
Snow
Diane M
DM
Roberts
Sally
S
D053674:Aggrecans; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D005727:Ganglia, Spinal / Q000166:cytology; D006026:Glycoside Hydrolases; D006801:Humans; D066298:In Vitro Techniques; D007403:Intervertebral Disc / Q000737:chemistry / Q000294:innervation*; D037181:Lectins, C-Type; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology*; D011509:Proteoglycans / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000494:pharmacology
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D006026:Glycoside Hydrolases; C026093:keratan-sulfate endo-1,4-beta-galactosidase; D001616:beta-Galactosidase; D019765:Chondroitin ABC Lyase