Pathological changes in the total knee joint during spontaneous knee osteoarthritis in guinea pigs at different months of age

doi:10.12307/2025.369

Abstract

Abstract: BACKGROUND: The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans.
OBJECTIVE: To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months.
METHODS: Eight healthy female Hartley guinea pigs in each age group of 1, 6, 10, 14, 16, and 18 months old were selected. The quadriceps femoris was taken for hematoxylin-eosin staining, and the total knee joint was stained with hematoxylin-eosin and toluidine blue. The histopathology of the cartilage, subchondral bone, synovium, meniscus, and muscles were observed under light microscope. Mankin’s score and synovitis score were compared, and the correlation analysis was conducted.
RESULTS AND CONCLUSION: As the guinea pig age increased, the Mankin’s score increased (P < 0.05), and the pathological score of synovitis also gradually increased (P < 0.05), and there was a significant positive correlation between the two (r=0.641, P < 0.001). The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%, and the incidence of meniscus injury was 37.5%. In addition, osteophyte and narrowing of the joint space were observed, and only a few guinea pigs had inflammation in the quadriceps femoris. To conclude, guinea pigs develop significant cartilage defects, synovial inflammation, subchondral bone lesions, meniscus injury, osteophyte formation, and joint space narrowing as they age, all of which are similar to the pathological processes of primary knee osteoarthritis in humans, making it an ideal model of spontaneous knee osteoarthritis.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: knee osteoarthritis, guinea pig, pathology, cartilage injury, synovitis, bone marrow lesion

CLC Number:

Hu Xiaoshen, Li Huijing, Lyu Junling, Xiao Xianjun, Li Juan, Li Xiang, Liu Ling, Jin Rongjiang. Pathological changes in the total knee joint during spontaneous knee osteoarthritis in guinea pigs at different months of age[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(11): 2218-2224.

Figures/Tables 3

2.1 实验动物数量分析实验选用豚鼠48只，实验过程均无死亡，全部进入结果分析。 2.2 体质量分析 1月龄豚鼠平均体质量为(92.0±8.7) g，6月龄体质量为(575.2±49.3) g，10月龄体质量为(660.3±81.2) g，14月龄体质量为(702.0±67.1) g，16月龄体质量为(738.3±65.2) g，18月龄体质量为(789.2±117.9) g。总体上呈现豚鼠年龄越大，体质量越大的趋势。 2.3 关节软骨病理评分比较关节软骨病理评分比较见图1。1月龄：软骨表面光滑，软骨细胞均匀分部，基质染色均匀；6月龄：软骨细胞出现分布不均匀，软骨表面不规则，浅层有缺损，浅层基质染色减少；10月龄：软骨细胞出现簇集，软骨浅层有缺损，可达中间层，浅层中间层基质染色均减少；14月龄：软骨细胞出现局部弥漫性增多或减少，软骨有较大裂隙，可达深层，基质3层均有较大范围染色减少；16月龄：软骨细胞弥漫性较少，软骨深层出现较大范围缺损，基质3层均有较大范围染色减少；18月龄：软骨细胞弥漫性较少，软骨出现较大范围缺损，有的可直达深层，甚至钙化层，基质3层均有大范围染色减少。从10月龄开始，豚鼠月龄越大，软骨下骨硬化越明显，骨小梁增多增粗，间隙变小，小梁由棒槌状变为板状。随着豚鼠月龄的增长，Mankin评分越高(P < 0.05)，软骨损伤越严重。 2.4 膝关节滑膜炎病理评分如图2所示，1月龄，存在少量绒毛增生；6月龄，滑膜内层细胞增生(3-5层)，少量绒毛增生，轻微的血管增生，淋巴细胞和中性粒细胞增多；10月龄，滑膜内层细胞增生(3-5层)，绒毛增生明显呈指状突起，血管增生明显，淋巴细胞和中性粒细胞增多；14月龄，滑膜内层细胞增生(≥6层)，血管增生明显；16月龄，血管增生显著，大量淋巴细胞和中性粒细胞浸润，滑膜基质纤维化；18月龄，滑膜内层细胞增生(3-5层)，绒毛增生明显呈指状突起，血管增生显著，大量淋巴细胞核中性粒细胞浸润；随着豚鼠月龄的增长，其滑膜炎病理评分呈逐渐增高趋势(P < 0.05)。 2.5 关节软骨Mankin评分与滑膜炎评分的相关性分析豚鼠的关节软骨Mankin评分与滑膜炎评分Pearson相关性分析结果显示：相关系数r=0.641，P < 0.001，二者存在显著的正相关关系，见表3。"

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