Intradiscal injection of monosodium iodoacetate induces intervertebral disc degeneration in an experimental rabbit model

Arthritis Research & Therapy

Koki Kawaguchi¹  Takao Sudo¹  Takahiro Hasegawa¹  Akihiro Sudo¹  Koji Akeda¹  Junichi Yamada¹  Koichi Masuda²  Nozomu Inoue³ 

[1] Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, 514-8507, Tsu City, Mie, Japan;Department of Orthopaedic Surgery, University of California, San Diego, 9500 Gilman Dr, 92093-0863, La Jolla, USA;Department of Orthopedic Surgery, Rush Medical College, 60612-3833, Chicago, IL, USA;

关键词: Intervertebral disc;    Disc degeneration;    Monosodium iodoacetate;    μCT;    MRI;    Histology;    Rabbit;    Animal model;   

DOI  :  10.1186/s13075-021-02686-6

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY