Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
Department of Orthopedic Surgery, Rush Medical College, Chicago, IL, 60612-3833, USA.
Arthritis Res Ther. 2021 Dec 8;23(1):297. doi: 10.1186/s13075-021-02686-6.
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 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.
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.
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 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.
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.
建立最佳的椎间盘（IVD）退变动物模型对于开发新的 IVD 治疗方法至关重要。单钠焦磷酸盐（MIA）关节内注射，常用于骨关节炎动物模型，可在剂量和时间依赖性方式下诱导软骨退变和进行性关节炎。本研究旨在通过放射学、微计算机断层扫描（micro-CT）、磁共振成像（MRI）和组织学分析来确定 MIA 注入兔 IVD 对 IVD 退变进展的影响。
本研究共使用 24 只新西兰白兔（NZW）。在全身麻醉下，从 L1-L2 到 L4-L5 的腰椎进行后外侧经皮 MIA 造影剂（CA）注射（L1-L2：仅 CA；L2-L3：MIA 0.01mg；L3-L4：0.1mg；L4-L5：1.0mg；L5-L6：非注射（NI）对照）。每隔两周对椎间盘高度进行放射学监测，直到注射后 12 周。注射后 2、4、8 和 12 周时，处死 6 只兔子并进行 micro-CT、MRI（T2 映射）和组织学分析。通过 micro-CT 数据的 3D 重建评估五个解剖区域的 3D 椎间盘高度。
MIA 注射椎间盘（L2-L3 至 L4-L5）的椎间盘高度随时间逐渐下降（P <0.0001）。MIA 0.01mg 注射椎间盘的椎间盘高度明显高于 MIA 0.1 和 1.0mg 注射椎间盘（P <0.01）。3D micro-CT 分析显示，MIA 注射椎间盘的 3D 椎间盘高度呈剂量和时间依赖性降低，主要发生在后环纤维（AF）区。与 CA 和/或 NI 对照组相比，MIA 0.1 和 1.0mg 注射椎间盘的 MRI T2 值明显降低（P <0.05）。组织学分析显示，MIA 注射的椎间盘随时间和剂量呈进行性退变变化（P <0.01）。MIA 诱导兔髓核细胞死亡，细胞克隆比例低。
本研究首次表明，MIA 椎间盘内注射可在时间和剂量依赖性方式下诱导兔 IVD 发生退行性变化。本研究表明，MIA 注入兔 IVD 可作为 IVD 退变的动物模型，用于开发未来的治疗方法。
