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Background: Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and timedependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses.Methods: In total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data.Results: Disc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P < 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P< 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIAinjected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P < 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P < 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low.Conclusions: The results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time-and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.
本文/Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2‑174 Edobashi, Tsu City, Mie 514‑8507, Japan
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DOIinfo:doi/10.1186/s13075-021-02686-6
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