A novel rabbit disc degeneration model induced by fibronectin fragment.

ABSTRACT

OBJECTIVE: To establish a novel and useful rabbit model of lumbar disc degeneration using microinjection of a fibronectin fragment. METHODS: Thirty-two rabbits underwent injection of N-terminal 30 kDa fibronectin fragment (Fn-f) (Group A, n=12; Group B, n=4) or phosphate buffered saline (PBS) (Group C, n=12; Group D, n=4) into the lumbar discs using a 32-gauge microsyringe. Two rabbits (Group E) with no treatment were sacrificed to examine the proteoglycan synthesis of neucleus pulposus (NP) using (35)S-sulfate incorporation assay. At the 4-, 8-, 12-, and 16-week time points, the discs were examined histologically, radiographically and with proteoglycan synthesis. RESULTS: (1) Histology demonstrated a progressive loss of cell numbers in NP and architecture disorganization in NP and annulus fibrosus (AF) over the study period. (2) Radiology comparing with the PBS-injected discs, the Fn-f-injected discs exhibited no significant differences in disc heights at the 4-week time point, but significant decreases in disc heights at the 8-, 12-, and 16-week time points (P<0.01). Apparent anterior osteophytes formed at the 12-week time point and enlarged remarkably by the 16-week time point in the Fn-f-injected spines. (3) Protoglycan synthesis in the Fn-f-injected discs decreased progressively (P<0.01). At each time point, the Fn-f-injected discs showed significantly decreased proteoglycan synthesis compared with controls (P<0.05 or P<0.01). CONCLUSIONS: Fn-f induced a progressively degenerative process in rabbit discs, which was consistent with the spontaneous degeneration in human. Fn-f induced degeneration seemed to be a novel and useful model for the study of disc degeneration at the molecular level.