A fibronectin fragment stimulates intervertebral disc degeneration in vivo.
METHODS
A radiographic, histologic, biochemical, and gene expression study was conducted in vivo in a rabbit model to determine the effect of injection of the N-terminal 30 kDa fibronectin fragment (Fn-f) into the intervertebral disc along with various control substances.


OBJECTIVE
To determine if the Fn-f is able to induce disc degeneration in vivo.


BACKGROUND
Animal models of disc degeneration are crucial to defining the molecular events involved in disc degeneration. Although spontaneous and induced models of disc degeneration have been described, none is ideal for molecular studies. A better understanding of disc degeneration at the molecular level is necessary to promote rational design of therapies for degenerative disc disease.


METHODS
Thirty-one New Zealand white rabbits underwent injection of Fn-f and control substances into the central region of separate lumbar discs using a fine needle. Euthanasia was performed at the 2-, 4-, 8-, 12-, and 16-week time points and the discs were examined radiographically, histologically, biochemically, and with gene expression.


RESULTS
Radiographs demonstrated anterior osteophyte formation at Fn-f-injected disc spaces by the 12-week time point. Histology demonstrated a progressive loss of the normal architecture of the nucleus pulposus and anulus fibrosus over the 16-week study period. A progressive loss of proteoglycans was documented using GAG assay but total collagen did not appear to change appreciably. Gene expression studies demonstrated a significant down-regulation of both aggrecan and type II collagen mRNA between the 8- and 16-week time points.


CONCLUSIONS
Fn-f appears to induce a progressive degenerative process within the intervertebral disc after injection that resembles degenerative disc disease. This model has several significant advantages for the study of disc degeneration at the molecular level. Further studies are warranted to elucidate the mechanism and molecular events associated with Fn-f-mediated disc degeneration.
Greg Anderson
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Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. dga3k@virginia.edu
Li
Xudong
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Tannoury
Tony
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Beck
Gina
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Balian
Gary
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D053674:Aggrecans; D000818:Animals; D024043:Collagen Type II / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011509:Proteoglycans / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006025:Glycosaminoglycans; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans; D006909:Hydroxyproline