Characterisation of growth plate dynamics in murine models of osteoarthritis

Characterisation of growth plate dynamics in murine models of osteoarthritis
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骨关节炎小鼠模型中生长板动力学的表征

DOI：
10.1101/2020.10.14.339119
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发表时间：
2020
期刊：
--
影响因子：
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通讯作者：
Samvelyan H
Samvelyan H
中科院分区：
--
文献类型：
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作者：
Samvelyan H

文献摘要

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本研究的目的是研究骨关节炎手术和负荷小鼠模型中的生长板动力学，以了解这些动力学的异常是否与骨关节炎的发展相关。8周龄的C57 BL/6雄性小鼠在右膝关节中经历内侧半月板（DMM）（n =8）去稳定化手术。左侧膝关节无干预（对照组）。在16周龄C57 BL/6雄性小鼠（n= 6）中，使用峰值力为11 N的右膝关节的非侵入性机械负荷诱导骨关节炎。非负荷左膝关节为内部对照。组织学和免疫组化证实胫骨关节软骨和生长板中的软骨细胞短暂。使用microCT测量胫骨软骨下骨参数，并与三维（3D）生长板桥接分析相关。软骨细胞肥大标志物Col 10a 1和MMP 13在DMM和负荷小鼠的胫骨关节软骨细胞中观察到更高的表达。与对照组相比，在DMM（分别为p=0.002和p <0.0001）和负荷（均为p <0.0001）小鼠胫骨生长板中，Col 10a 1和MMP 13在增殖和肥大软骨细胞显著扩大的区域中广泛表达。3D定量显示，与DMM的外侧胫骨和小鼠的负荷膝关节相比，内侧的生长板桥接和更高的桥接密度富集。生长板动力学与DMM和负荷膝关节内侧胫骨软骨下骨体积分数（BV/TV; %）增加以及负荷膝关节内侧胫骨骺骨小梁体积分数增加相关。结果证实了关节软骨软骨细胞在骨关节炎的手术和负荷鼠模型中的瞬时性。在此，我们揭示了手术和负荷骨关节炎模型中生长板桥接的空间变化，以及这些可能如何导致骨关节炎发展脆弱性的解剖学变化。
The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n =8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n= 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (p=0.002 andp<0.0001, respectively) and loaded (bothp<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.