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Effects of Mild and Moderate Monoclonal Antibody Dose on Inflammation, Bone Loss, and Activation of the Central Nervous System in a Female Collagen Antibody-induced Arthritis Mouse Model
Journal of Histochemistry & Cytochemistry ( IF 3.2 ) Pub Date : 2021-07-22 , DOI: 10.1369/00221554211033562
Bonnie Williams 1 , Florence Lees 1, 2 , Helen Tsangari 1 , Mark R Hutchinson 1, 2 , Egon Perilli 3 , Tania N Crotti 1
Affiliation  

Induction of severe inflammatory arthritis in the collagen antibody-induced arthritis (CAIA) murine model causes extensive joint damage and pain-like behavior compromising analysis. While mild models are less severe, their reduced, variable penetrance makes assessment of treatment efficacy difficult. This study aimed to compare macroscopic and microscopic changes in the paws, along with central nervous system activation between a mild and moderate CAIA model. Balb/c mice (n=18) were allocated to control, mild, and moderate CAIA groups. Paw inflammation, bone volume (BV), and paw volume (PV) were assessed. Histologically, the front paws were assessed for joint inflammation, cartilage damage, and pre/osteoclast-like cells and the lumbar spinal cord and the periaqueductal gray (PAG) region of the brain for glial reactivity. A moderate CAIA dose induced (1) significantly greater local paw inflammation, inflammatory cell infiltration, and PV; (2) significantly more osteoclast-like cells on the bone surface and within the surrounding soft tissue; and (3) significantly greater glial reactivity within the PAG compared with the mild CAIA model. These findings support the use of a moderate CAIA model (higher dose of monoclonal antibodies with low-dose lipopolysaccharide) to induce more consistent histopathological features, without excessive joint destruction.



中文翻译:

轻度和中度单克隆抗体剂量对雌性胶原抗体诱导的关节炎小鼠模型中中枢神经系统炎症、骨丢失和激活的影响

在胶原抗体诱导的关节炎 (CAIA) 小鼠模型中诱导严重的炎症性关节炎会导致广泛的关节损伤和疼痛样行为损害分析。虽然轻度模型不太严重,但它们降低的、可变的外显率使得治疗效果的评估变得困难。本研究旨在比较轻度和中度 CAIA 模型之间爪子的宏观和微观变化,以及中枢神经系统的激活。Balb/c 小鼠 ( n=18) 被分配到对照组、轻度和中度 CAIA 组。评估爪炎症、骨体积 (BV) 和爪体积 (PV)。组织学上,评估前爪的关节炎症、软骨损伤和前/破骨细胞样细胞以及腰脊髓和大脑的导水管周围灰质 (PAG) 区域的神经胶质反应性。中等 CAIA 剂量诱导 (1) 明显更大的局部爪子炎症、炎性细胞浸润和 PV;(2) 骨表面和周围软组织内的破骨细胞样细胞明显增多;(3) 与轻度 CAIA 模型相比,PAG 内的神经胶质反应性显着增加。这些发现支持使用中等 CAIA 模型(高剂量的单克隆抗体和低剂量脂多糖)来诱导更一致的组织病理学特征,

更新日期:2021-07-22
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