Abstract
BackgroundEstablishing 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 time-dependent 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.MethodsIn 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.ResultsDisc 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 MIA-injected 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.ConclusionsThe 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.
Highlights
Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies
The intradiscal injection of monosodium iodoacetate (MIA) 0.01 mg induced a significant decrease of %disc height index (DHI) to approximately 87% of baseline at 4 weeks post-injection; this continued to decrease to approximately 81% at 12 weeks post-injection
For the first time, we have shown that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs evaluated by radiography, computed tomography (CT), magnetic resonance imaging (MRI), and histology
Summary
Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. Sudo et al Arthritis Research & Therapy (2021) 23:297 intervertebral disc (IVD) degeneration is an important cause of pain in LBP patients [2, 3]. It is important to establish an optimal animal model for IVD degeneration that mimics the biological process of human IVD degeneration in order to elucidate the pathological mechanisms of degenerative disc diseases and to develop novel treatments for them. With increasing age or degeneration, there is an increase in cell proliferation (formation of cell clusters) and an increase in cell death [7] These cellular changes are accompanied by biochemical changes in the ECM constituents, including a decrease in water and PG content that leads to tissue fibrosis in the NP [4]
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