Histological scoring system for subchondral bone changes in murine models of joint aging and osteoarthritis
Histological scoring system for subchondral bone changes in murine models of joint aging and osteoarthritis
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DOI：
10.1038/s41598-020-66979-7
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发表时间：
2020-06-22
影响因子：
4.6
通讯作者：
Lotz, Martin
中科院分区：
文献类型：
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作者：
Nagira, Keita;Ikuta, Yasunari;Lotz, Martin
为了建立膝骨性关节炎(OA)模型小鼠软骨下骨改变的组织病理学评分系统，选择了软骨下骨板(Subcho.BP)三个关键参数，包括软骨下骨板厚度(Subcho.BP.Th)和血管生成、骨体积(BV/Tv)和骨赘。新的分级系统在两个小鼠OA模型上进行了测试，(1)作为自发性骨关节炎模型的衰老加速小鼠(SAM)倾向8(SAMP8)，作为对照(SAMR1)；(2)C57BL/6小鼠内侧半月板失稳作为外科骨关节炎模型。自发性骨关节炎模型结果显示，SAMP8组较SAMR1组BP.Th亚组明显增宽，血管生成明显增多，BV/TV值较高。值得注意的是，在6周时，SAMP8组的软骨下骨评分显著高于SAMR1组，而OARSI软骨评分仅在14周时变得更高。在手术骨关节炎模型中，结果与自发性骨关节炎模型相似，但骨赘出现得更早。BP.Th和Bv/Tv与MUCT之间均有较强的相关性(r分别为0.89和0.84)。使用该系统的每个参数的评分员间信度都在0.943以上。我们的结论是，这种新的组织病理学评分系统很容易适用于评估衰老和骨关节炎影响的小鼠软骨下骨的早期变化。
To establish a histopathological scoring system for changes in subchondral bone in murine models of knee osteoarthritis (OA), three key parameters, subchondral bone plate (Subcho.BP) consisting of the combination of Subcho.BP.thickness (Subcho.BP.Th) and angiogenesis, bone volume (BV/TV) and osteophytes, were selected. The new grading system was tested in two mouse OA models, (1) senescence accelerated mouse (SAM)-prone 8 (SAMP8) as spontaneous OA model with SAM-resistant 1 (SAMR1) as control; (2) destabilization of the medial meniscus in C57BL/6 mice as surgical OA model. Results of the spontaneous OA model showed that Subcho.BP.Th was significantly wider, angiogenesis was greater, and BV/TV was higher in SAMP8 than SAMR1. Notably, subchondral bone score was dramatically higher in SAMP8 at 6 weeks than SAMR1, while OARSI cartilage scores became higher only at 14 weeks. In the surgical OA model, the results were similar to the spontaneous OA model, but osteophytes appeared earlier. There were strong correlations both in Subcho.BP.Th and BV/TV between this scoring system and mu CT (r=0.89, 0.84, respectively). Inter-rater reliabilities for each parameter using this system were more than 0.943. We conclude that this new histopathological scoring system is readily applicable for evaluating the early changes in aging and OA-affected murine subchondral bone.