Intradiscal injection of monosodium iodoacetate induces intervertebral disc degeneration in an experimental rabbit model.
Intradiscal injection of monosodium iodoacetate induces intervertebral disc degeneration in an experimental rabbit model.
复制标题
DOI：
10.1186/s13075-021-02686-6
复制
发表时间：
2021-12-08
影响因子：
4.9
通讯作者：
Sudo A
中科院分区：
文献类型：
--
作者：
Sudo T;Akeda K;Kawaguchi K;Hasegawa T;Yamada J;Inoue N;Masuda K;Sudo A
建立椎间盘（IVD）退变的最佳动物模型对于开发新的 IVD 疗法至关重要。关节内注射碘乙酸一钠（MIA）常用于骨关节炎动物模型，以剂量和时间依赖性方式诱导软骨变性和进行性关节炎。本研究的目的是通过放射线照相、微型计算机断层扫描 (micro-CT)、磁共振成像 (MRI) 和组织学分析来确定兔 IVD 注射 MIA 对 IVD 变性进展的影响。本研究总共使用了 24 只新西兰白兔 (NZW)。在全身麻醉下，从L1-L2到L4-L5的腰椎间盘后外侧经皮注射MIA造影剂（CA）（L1-L2：仅CA；L2-L3：MIA 0.01 mg；L3-L4：0.1 mg；L4-L5：1.0 mg；L5-L6：非注射（NI）对照）。每两周对椎间盘高度进行放射学监测，直至注射后 12 周。注射后 2、4、8 和 12 周处死 6 只兔子，并进行显微 CT、MRI（T2 映射）和组织学分析。通过显微 CT 数据的 3D 重建来评估五个解剖区域的三维 (3D) 椎间盘高度。注射 MIA 的椎间盘高度（L2-L3 至 L4-L5）随时间逐渐下降（P < 0.0001）。注射MIA 0.01 mg的椎间盘高度显着高于注射MIA 0.1和1.0 mg的椎间盘（分别P < 0.01）。 3D 显微 CT 分析显示，注射 MIA 的椎间盘的 3D 椎间盘高度呈剂量和时间依赖性下降，主要发生在后纤维环 (AF) 区域。与 CA 和/或 NI 对照相比，注射 MIA 0.1 和 1.0 mg 的椎间盘的 MRI T2 值显着降低（P < 0.05）。组织学分析显示注射 MIA 的椎间盘出现渐进的时间和剂量退行性变化（P < 0.01）。 MIA诱导兔髓核细胞死亡的比例较高，而细胞克隆的比例较低。这项研究的结果首次表明，椎间盘内注射MIA会以时间和剂量依赖性方式诱导兔IVD的退行性变化。这项研究表明，将 MIA 注射到兔 IVD 中可以作为 IVD 退化的动物模型，用于开发未来的治疗方法。
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.
登录
查看更多内容
影响因子：
3
作者：
TSUJI, H;HIRANO, N;MOTOE, T
通讯作者：
MOTOE, T
影响因子：
3.7
作者：
Gullbrand SE;Ashinsky BG;Lai A;Gansau J;Crowley J;Cunha C;Engiles JB;Fusellier M;Muehleman C;Pelletier M;Presciutti S;Schol J;Takeoka Y;Yurube T;Zhang Y;Masuda K;Iatridis JC
通讯作者：
Iatridis JC
影响因子：
2.3
作者：
Akeda K;Yamada T;Inoue N;Nishimura A;Sudo A
通讯作者：
Sudo A
影响因子：
--
作者：
Guingamp, C;GegoutPottie, P;Gillet, P
通讯作者：
Gillet, P
影响因子：
17.3
作者：
PAZZAGLIA, UE;SALISBURY, JR;BYERS, PD
通讯作者：
BYERS, PD