Assessment of osteoarthritis functional outcomes and intra-articular injection volume in the rat anterior cruciate ligament transection model.

Assessment of osteoarthritis functional outcomes and intra-articular injection volume in the rat anterior cruciate ligament transection model.
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DOI:
10.1002/jor.25245
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发表时间:
2022-09
影响因子:
2.8
通讯作者:
Reesink, Heidi L.
Reesink, Heidi L.
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Yuyan;Wagner, Emma S.;Yu, Danqiao;Chen, Kevin J.;Keel, Taidhgin J.;Pownder, Sarah L.;Koff, Matthew F.;Cheetham, Jonathan;Samaroo, Kirk J.;Reesink, Heidi L.

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大鼠手术前交叉韧带横断(ACLT)模型通常用于研究关节内骨关节炎(OA)治疗,组织学评估通常是主要结果指标。然而,组织学变化并不总是与临床结果良好相关。因此,本研究评估了大鼠手术 ACLT 模型的功能结果,并比较了 20 至 50 μL 范围内的关节内注射体积。通过手术诱导单侧 ACLT,并对 4 组雄性 Sprague-Dawley 大鼠(每组 6 只)进行静态负重、机械异常性疼痛、运动功能和步态评估。术后每周一次关节内注射 20 μL Dulbecco 磷酸盐缓冲盐水 (DPBS)、50 μL DPBS 或 50 μL 合成仿生边界润滑剂,持续 3 周。 20周时对结构变化进行组织学评估。向大鼠尸体膝盖注射 20、30、40 或 50 μl 钆溶液,并使用磁共振成像 (MRI) 进行成像。 ACLT 组的静态负重、机械异常性疼痛和步态参数显示 ACLT 后 4 周与基线和初始对照组的差异;然而,这些差异并没有持续超过 6 周。不同的DPBS关节内注射量不会导致功能或组织学变化;然而,在注射 50、40 和 30 μl 钆(而非 20 μl)后,通过 MRI 记录了关节周围渗漏。尽管有证据表明 20 周时存在中度组织学 OA,但功能参数的差异主要限于大鼠 ACLT 手术模型的早期、术后变化。 20-30 μl 的注射量更适合研究大鼠膝关节内治疗。
The rat surgical anterior cruciate ligament transection (ACLT) model is commonly used to investigate intra-articular osteoarthritis (OA) therapies, and histological assessment is often the primary outcome measure. However, histological changes do not always correlate well with clinical outcomes. Therefore, this study evaluated functional outcomes in the rat surgical ACLT model and compared intra-articular injection volumes ranging from 20 to 50 μL. Unilateral ACLT was surgically induced, and static weight-bearing, mechanical allodynia, motor function, and gait were assessed in 4 groups of male, Sprague-Dawley rats (n = 6 per group). Intra-articular injections of 20 μL Dulbecco’s phosphate-buffered saline (DPBS), 50 μL DPBS or 50 μL of synthetic biomimetic boundary lubricant were administered once weekly for 3 weeks post-operatively. Structural changes were evaluated histologically at 20 weeks. Rat cadaver knees were injected with 20, 30, 40, or 50 μl of gadolinium solutions and were imaged using magnetic resonance imaging (MRI). Static weight-bearing, mechanical allodynia, and gait parameters in ACLT groups revealed differences from baseline and naïve controls for 4 weeks post-ACLT; however, these differences did not persist beyond 6 weeks. Different intra-articular DPBS injection volumes did not result in functional or histological changes; however, peri-articular leakage was documented via MRI following 50, 40, and 30 μl but not 20 μl gadolinium injections. Differences in functional parameters were predominantly restricted to early, postoperative changes in the rat surgical ACLT model despite evidence of moderate histologic OA at 20 weeks. Injection volumes of 20–30 μl are more appropriate for investigating intra-articular therapies in the rat knee.
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